Cited by 1,779Bone health and osteoporosis researchBone Metabolism and DiseasesAlkaline Phosphatase Research Studies

The DOI matches its Crossref record; 133 of the 145 references it cites were found in a registry or an index; 16 of the 80 sources its claims cite were checked for support.

Pathogenesis of osteoporosis: concepts, conflicts, and prospects

Open access

Raisz, L. G.·2005·Journal of Clinical Investigation

DOI 10.1172/jci27071PMC PMC1297264

Open this paper in CoChat — free account Open PDF

Abstract

Osteoporosis is a disorder in which loss of bone strength leads to fragility fractures. This review examines the fundamental pathogenetic mechanisms underlying this disorder, which include: (a) failure to achieve a skeleton of optimal strength during growth and development; (b) excessive bone resorption resulting in loss of bone mass and disruption of architecture; and (c) failure to replace lost bone due to defects in bone formation. Estrogen deficiency is known to play a critical role in the development of osteoporosis, while calcium and vitamin D deficiencies and secondary hyperparathyroidism also contribute. There are multiple mechanisms underlying the regulation of bone remodeling, and these involve not only the osteoblastic and osteoclastic cell lineages but also other marrow cells, in addition to the interaction of systemic hormones, local cytokines, growth factors, and transcription factors. Polymorphisms of a large number of genes have been associated with differences in bone mass and fragility. It is now possible to diagnose osteoporosis, assess fracture risk, and reduce that risk with antiresorptive or other available therapies. However, new and more effective approaches are likely to emerge from a better understanding of the regulators of bone cell function.

Integrity signals

Registry

Crossref · 10.1172/jci27071

Cites

133 of 133 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

16 of 80 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

Every source the paper cites for this claim was checked and supports it.
In the paper
“estrogen has a greater effect than androgen in inhibiting bone resorption in men”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Central role of estrogen
What the sources say
- Supported
  The paper reports that estrogen played the major role in preventing an increase in bone-resorption markers, while testosterone had no statistically significant effect (p. 1). It concludes that estrogen is the dominant sex steroid regulating bone resorption in normal elderly men (p. 7). (LLM, conf=0.93)
  cites [15] 15. Falahati-Nini, A., et al. 2000. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J. Clin. Invest. 106:1553-1560. source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the largest study to date, in Icelandic and Danish cohorts, suggests that polymorphisms of the BMP2 gene are linked to low BMD and fracture risk”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Local and systemic growth factors
What the sources say
- Partly supported
  The Abstract and Results (Haplotype Confirmation in Danish Cohort; page numbers unavailable) report BMP2-variant associations with low BMD and osteoporotic fractures in Icelandic patients, with supporting results in a Danish cohort. The copy describes a large Icelandic study but does not establish that it was the largest study to date. (LLM, conf=0.82)
  cites [79] 79. Styrkarsdottir, U., et al. 2003. Linkage of osteo- porosis to chromosome 20p12 and association to BMP2. PLoS Biol. 1:E69. sourceExperimental — accuracy not yet measured
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
Every source the paper cites for this claim was checked and supports it.
In the paper
“RANKL levels were increased on the surface of bone marrow cells from early postmenopausal women who are estrogen deficient”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Receptor activator of NF-κB, its ligand, and osteoprotegerin
What the sources say
- Supported
  The Introduction (p. 2) reports increased surface expression of RANKL on bone marrow cells from untreated early postmenopausal women compared with estrogen-replete women. The Discussion (p. 8) identifies the untreated group as estrogen deficient and reports a two- to threefold increase in the measure of cell-surface RANKL. (LLM, conf=0.95)
  cites [48] 48. Eghbali-Fatourechi, G., et al. 2003. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J. Clin. Invest. 111:1221-1230. doi:10.1172/JCI200317215. source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A mutation of LRP5 that leads to constitutive activation can result in an increase in bone density”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Genes determining osteoblast differentiation and function
What the sources say
- Partly supported
  Section 6 says the LRP5 gain-of-function mutation described by the authors produces increased bone mass. It does not establish that the mutation causes constitutive activation; its discussion of how the mutation affects protein interactions is tentative. (LLM, conf=0.88)
  cites [58] 58. Little, R.D., et al. 2002. A mutation in the LDL receptor-related protein 5 gene results in the auto- somal dominant high-bone-mass trait. Am. J. Hum. Genet. 70:11-19. sourceExperimental — accuracy not yet measured
- Not checked — no full text of the sourcecites [59] 59. Boyden, L.M., et al. 2002. High bone density due to a mutation in LDL-receptor-related protein 5. N. Engl. J. Med. 346:1513-1521. source
Load-bearingStrength:plain· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“locally produced cytokines such as IL-1 and prostaglandins such as prostaglandin E 2 (PGE 2 ) can affect bone”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Cytokines, prostaglandins, NO, and leukotrienes
What the sources say
- Not checked — no full text of the sourcecites [81] 81. Klein, D.C., and Raisz, L.G. 1970. Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology. 86:1436-1440. source
- Partly supported
  The Discussion reports that osteoclast-activating factor (OAF) secreted by human leukocytes stimulates bone resorption in fetal rat bone cultures, and that PGE2 can also affect resorption. It does not identify OAF as IL-1 or establish that PGE2 is locally produced. The claim's specific IL-1 and local-production details are therefore unsupported by this copy. (LLM, conf=0.84)
  cites [82] 82. Raisz, L.G., et al. 1975. Effect of osteoclast activat- ing factor from human leukocytes on bone metab- olism. J. Clin. Invest. 56:408-413. sourceExperimental — accuracy not yet measured
Load-bearingStrength:plain· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“A polymorphism of the first intron of the gene coding for the type I collagen α1 chain and increased levels of homocysteine can influence fracture risk independent of BMD”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Collagen abnormalities
What the sources say
- Partly supported
  The results passage (indexed under “covariables”; page unavailable) associates higher homocysteine levels with greater hip-fracture risk in older men and women. The discussion says baseline BMD data were unavailable, so the study could not determine whether that association was independent of BMD. The paper does not address the claimed type I collagen α1 first-intron polymorphism. (LLM, conf=0.91)
  cites [100] 100. McLean, R.R., et al. 2004. Homocysteine as a pre- dictive factor for hip fracture in older persons. N. Engl. J. Med. 350:2042-2049. 102. van Meurs, J.B., et al. 2004. Homocysteine levels and the risk of osteoporotic fracture. N. Engl. J. Med. 350:2033-2041. 103. Ducy, P., et al. 2000. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell. 100:197-207. 104. sourceExperimental — accuracy not yet measured
- Not checked — no full text of the sourcecites [101] 101. Elefteriou, F., et al. 2005. Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature. 434:514-520. 105. Takeda, S. 2005. Central control of bone remodel- ing. Biochem. Biophys. Res. Commun. 328:697-699. 106. source
- Not checked — no full text of the sourcecites [102] 102. Pasco, J.A., et al. 2004. Beta-adrenergic blockers reduce the risk of fracture partly by increasing bone mineral density: Geelong Osteoporosis Study. J. Bone Miner. Res. 19:19-24. 107. source
Load-bearingStrength:plain· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Increased β-adrenergic activity can decrease bone mass, but other neural pathways may be involved (104, 105).”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Leptin and neural pathways
What the sources say
- Could not verify
  The Introduction (page unavailable) says neuroendocrine pathways and neurotransmitters regulate bone remodelling, but does not identify β-adrenergic activity. The Results and Discussion (pages unavailable) address cannabinoid receptors and bone mass; searches for β-adrenergic activity and sympathetic signalling found no passage supporting the specific claim. (LLM, conf=0.74)
  cites [104] 104. Idris, A.I., et al. 2005. Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat. Med. 11:774-799. 109. Raisz, L.G. 2005. Clinical practice. Screening for osteoporosis. N. Engl. J. Med. 353:164-171. 110. Benito, M., et al. 2003. Deterioration of trabecular architecture in hypogonadal men. J. Clin. Endocri- nol. Metab. 88:1497-1502. 111. Office of the Surgeon General. 2004. Bone health and osteoporosis: a report of the Surgeon General. US Department of Health and Human Services. Rockville, Maryland, USA. 404 pp. 112. Rosen, C.J. 2005. Clinical practice. Po sourceExperimental — accuracy not yet measured
- Not checked — no full text of the sourcecites [105] 105. Neer, R.M., et al. 2001. Effect of parathyroid hor- mone (1-34) on fractures and bone mineral den- sity in postmenopausal women with osteoporosis. N. Engl. J. Med. 344:1434-1441. 117. Meunier, P.J., et al. 2004. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N. Engl. J. Med. 350:459-468. 118. source
Load-bearingStrength:plain· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Leptin deficiency or resistance is associated with high BMD in mice despite the fact that gonadal function is diminished (103).”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Leptin and neural pathways
What the sources say
- Could not verify
  The Introduction (page unavailable) says leptin affects bone formation and bone mass in mice, but does not discuss leptin deficiency or resistance, high BMD in those mice, or diminished gonadal function. Searches for the claimed combination and for gonadal function found no passage addressing it. (LLM, conf=0.72)
  cites [103] 103. Reid, I.R., et al. 2005. beta-Blocker use, BMD, and fractures in the study of osteoporotic fractures. J. Bone Miner. Res. 20:613-618. 108. sourceExperimental — accuracy not yet measured
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes

Show all 44 claims

It may state two separate claims as one. 32
Probably not a substantial claim. 1

The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“the critical role for the Wnt signaling pathway in regulating osteoblast function is of particular interest, since it has been shown to play an important role in determining bone mass and strength”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Genes determining osteoblast differentiation and function
What the sources say
- Partly supported
  The discussion (section 6) reports that LRP5 participates in Wnt signaling and that an LRP5 mutation increases bone mass; it also reports enhanced skeletal strength in transgenic mice. It describes Wnt as important in skeletal differentiation, but does not directly establish that Wnt signaling regulates osteoblast function or itself determines bone mass and strength. (LLM, conf=0.84)
  cites [58] 58. Little, R.D., et al. 2002. A mutation in the LDL receptor-related protein 5 gene results in the auto- somal dominant high-bone-mass trait. Am. J. Hum. Genet. 70:11-19. sourceExperimental — accuracy not yet measured
- Not checked — no full text of the sourcecites [59] 59. Boyden, L.M., et al. 2002. High bone density due to a mutation in LDL-receptor-related protein 5. N. Engl. J. Med. 346:1513-1521. source
- Supported
  The Figure 3 passage describes LRP5 as a Wnt coreceptor required for osteoblast proliferation and function, and says its signaling pathway is important in regulating bone mass. The same section reports that children with inactivating LRP5 mutations have very low bone mass and are highly susceptible to fractures, supporting the claim about bone strength. Page numbers are unavailable in our copy. (LLM, conf=0.86)
  cites [60] 60. Van Wesenbeeck, L., et al. 2003. Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am. J. Hum. Genet. 72:763-771. source
- Not checked — no full text of the sourcecites [61] 61. Gong, Y., et al. 2001. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 107:513-523. source
Load-bearingStrength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“sclerostin, the product of the SOST gene, has been shown to inhibit both BMP2 and Wnt signaling”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Genes determining osteoblast differentiation and function
What the sources say
- Partly supported
  The paper identifies sclerostin as the SOST gene product and demonstrates that it inhibits canonical Wnt signaling. In Results and Discussion (page not specified), it discusses earlier reports of BMP antagonism but questions whether sclerostin functionally inhibits BMP signaling; it does not establish inhibition of BMP2 specifically. (LLM, conf=0.90)
  cites [70] 70. Li, X., et al. 2005. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem. 280:19883-19887. sourceExperimental — accuracy not yet measured
- Partly supported
  The Results section reports that sclerostin reduced BMP-6- and Wnt-3A-induced alkaline phosphatase activity in C3H10T1/2 cells; it does not establish inhibition of BMP-2 specifically. The Discussion says the Wnt-related effect was indirect, through BMP inhibition, and that sclerostin did not block early Wnt signaling measured by β-catenin accumulation. Page numbers are unavailable in our copy. (LLM, conf=0.88)
  cites [71] 71. Winkler, D.G., et al. 2004. Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by BMP proteins. J. Biol. Chem. 280:2498-2502. sourceExperimental — accuracy not yet measured
Strength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“overexpression of OPG produced osteopetrosis, while OPG-knockout mice had a phenotype of severe osteoporosis with a high incidence of fractures”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Receptor activator of NF-κB, its ligand, and osteoprotegerin
What the sources say
- Supported
  The Discussion reports increased bone density in OPG-overexpressing mice and severe bone loss in OPG-knockout mice. The Results report an increased incidence of fractures in the knockout mice, supporting the claimed phenotype. (LLM, conf=0.92)
  cites [46] 46. Bucay, N., et al. 1998. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev. 12:1260-1268. source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Vitamin D deficiency and secondary hyperparathyroidism can contribute not only to accelerated bone loss and increasing fragility, but also to neuromuscular impairment that can increase the risk of falls”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Calcium, vitamin D, and parathyroid hormone
What the sources say
- Not checked — no full text of the sourcecites [33] 33. Bischoff-Ferrari, H.A., et al. 2004. Effect of vitamin D on falls: a meta-analysis. JAMA. 291:1999-2006. source
- Partly supported
  The Introduction (page unavailable) says vitamin D deficiency may increase fall risk through neuromuscular effects and that secondary hyperparathyroidism occurs with vitamin D deficiency. The Discussion (page unavailable) reports associations between PTH, diminished muscle function, and falls. The paper does not address accelerated bone loss or increasing bone fragility, so those parts of the claim are unsupported. (LLM, conf=0.88)
  cites [34] 34. Sambrook, P.N., et al. 2004. Serum parathyroid hormone predicts time to fall independent of vita- min D status in a frail elderly population. J. Clin. Endocrinol. Metab. 89:1572-1576. sourceExperimental — accuracy not yet measured
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Inactivating mutations of this gene can produce the high-bone-mass disorder Van Buchem disease or sclerosteosis”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Genes determining osteoblast differentiation and function
What the sources say
- Partly supported
  The Abstract states that sclerosteosis patients carry SOST-null mutations, but Van Buchem patients have no SOST coding mutations; instead, they carry a noncoding deletion downstream of SOST. The Discussion explains that this deletion removes a SOST regulatory element and reduces its expression in adult bone. Thus, the paper supports SOST inactivation in both disorders, but not an inactivating mutation of the gene itself in Van Buchem disease. (LLM, conf=0.87)
  cites [72] 72. Loots, G.G., et al. 2005. Genomic deletion of a long- range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res. 15:928-935. sourceExperimental — accuracy not yet measured
- Partly supported
  The Introduction and Discussion identify loss-of-function SOST mutations as causative for sclerosteosis, a disorder of increased bone formation. The Mutation analysis section found no SOST mutation in the Dutch van Buchem family; the Discussion proposes a regulatory explanation but does not establish that SOST-inactivating mutations cause van Buchem disease. Page numbers are unavailable in our copy. (LLM, conf=0.90)
  cites [73] 73. Balemans, W., et al. 2001. Increased bone den- sity in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum. Mol. Genet. 10:537-543. sourceExperimental — accuracy not yet measured
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since osteoporosis is a complex, polygenic disorder, the contributions of specific gene polymorphisms are likely to be relatively small, but may still be clinically important.”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Abstract
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Osteoporosis is a complex polygenic disorder.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“NO is produced by bone cells and is a cofactor for the anabolic response to mechanical loading”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Cytokines, prostaglandins, NO, and leukotrienes
What the sources say
- Not checked — no full text of the sourcecites [91] 91. Bakker, A.D., et al. 2004. Additive effects of estro- gen and mechanical stress on nitric oxide and prostaglandin E(2) production by bone cells from osteoporotic donors. Osteoporos. Int. 16:983-989. source
- Not checked — no full text of the sourcecites [94] 94. Chow, J.W., Fox, S.W., Lean, J.M., and Chambers, T.J. 1998. Role of nitric oxide and prostaglandins in mechanically induced bone formation. J. Bone Miner. Res. 13:1039-1044. source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Gene deletion studies have shown that absence of runt-related transcription factor 2 (Runx2) or a downstream factor, osterix, are critical for osteoblast differentiation”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Genes determining osteoblast differentiation and function
What the sources say
- Not checked — no full text of the sourcecites [55] 55. Ducy, P., Zhang, R., Geoffroy, V., Ridall, A.L., and Karsenty, G. 1997. Osf2/Cbfa1: a transcrip- tional activator of osteoblast differentiation. Cell. 89:747-754. source
- Not checked — no full text of the sourcecites [56] 56. Nakashima, K., et al. 2002. The novel zinc finger- containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 108:17-29. source
Strength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“There is some association between BMD and the incidence of osteoporotic fractures and polymorphisms in the genes encoding IGF-1 and TGF-β”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Local and systemic growth factors
What the sources say
- Not checked — no full text of the sourcecites [76] 76. Lau, E.M., et al. 2004. Osteoporosis and trans- forming growth factor-beta-1 gene polymorphism in Chinese men and women. J. Bone Miner. Metab. 22:148-152. source
- Not checked — no full text of the sourcecites [77] 77. Langdahl, B.L., Carstens, M., Stenkjaer, L., and Erik- sen, E.F. 2003. Polymorphisms in the transforming growth factor beta 1 gene and osteoporosis. Bone. 32:297-310. source
- Not checked — no full text of the sourcecites [78] 78. Kim, J.G., Roh, K.R., and Lee, J.Y. 2002. The relation- ship among serum insulin-like growth factor-I, insu- lin-like growth factor-I gene polymorphism, and bone mineral density in postmenopausal women in Korea. Am. J. Obstet. Gynecol. 186:345-350. source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Estrogen acts through 2 receptors: estrogen receptor α (ERα) and ERβ.ERα appears to be the primary mediator of estrogen's actions on the skeleton”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Central role of estrogen
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [10] 10. Lee, K., Jessop, H., Suswillo, R., Zaman, G., and Lanyon, L. 2003. Endocrinology: bone adapta- tion requires oestrogen receptor-alpha. Nature. 424:389.
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Deletion of LRP5 results in a severe osteoporotic syndrome”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Genes determining osteoblast differentiation and function
What the sources say
- Not checked — no full text of the sourcecites [61] 61. Gong, Y., et al. 2001. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 107:513-523. source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Decreased calcium intake, impaired intestinal absorption of calcium due to aging or disease, as well as vitamin D deficiency can result in secondary hyperparathyroidism.”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Calcium, vitamin D, and parathyroid hormone
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [32] 32. Lips, P. 2001. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic impli- cations. Endocr. Rev. 22:477-501.
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Fracture risk is inversely related to estrogen levels in postmenopausal women, and as little as one-quarter of the dose of estrogen that stimulates the breast and uterus is sufficient to decrease bone resorption and increase bone mass in older women”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Central role of estrogen
What the sources say
- Not checked — no full text of the sourcecites [13] 13. Prestwood, K.M., Kenny, A.M., Kleppinger, A., and Kulldorff, M. 2003. Ultralow-dose micron- ized 17beta-estradiol and bone density and bone metabolism in older women: a randomized con- trolled trial. JAMA. 290:1042-1048. source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Stimulators of bone resorption have been found to increase RANKL expression in osteoblasts, and some also decrease OPG expression”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Receptor activator of NF-κB, its ligand, and osteoprotegerin
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [43] 43. Suda, T., et al. 1999. Modulation of osteoclast dif- ferentiation and function by the new members of the tumor necrosis factor receptor and ligand fami- lies. Endocr. Rev. 20:345-357.
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Clinical trials involving older individuals at high risk for calcium and vitamin D deficiency indicate that supplementation of both can reverse secondary hyperparathyroidism, decrease bone resorption, increase bone mass, decrease fracture rates, and even decrease the frequency of falling”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Calcium, vitamin D, and parathyroid hormone
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [32] 32. Lips, P. 2001. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic impli- cations. Endocr. Rev. 22:477-501.
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“the increased bone formation that normally occurs in response to mechanical loading is diminished in estrogen deficiency, suggesting estrogen is both anti-catabolic and anabolic”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Central role of estrogen
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [10] 10. Lee, K., Jessop, H., Suswillo, R., Zaman, G., and Lanyon, L. 2003. Endocrinology: bone adapta- tion requires oestrogen receptor-alpha. Nature. 424:389.
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Bone loss after ovariectomy in rodent models can be prevented by inhibiting IL-1 or TNF-α and does not occur in mice deficient in the IL-1 receptor or TNF-α”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Figure 1
What the sources say
- Not checked — no full text of the sourcecites [26] 26. Kimble, R.B., et al. 1995. Simultaneous block of interleukin-1 and tumor necrosis factor is required to completely prevent bone loss in the early post- ovariectomy period. Endocrinology. 136:3054-3061. source
- Not checked — no full text of the sourcecites [27] 27. Lorenzo, J.A., et al. 1998. Mice lacking the type I interleukin-1 receptor do not lose bone mass after ovariectomy. Endocrinology. 139:3022-3025. source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“bone remodeling is accelerated at the menopause, as both markers of resorption and formation are increased”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Central role of estrogen
What the sources say
- Not checked — no full text of the sourcecites [8] 8. Parfitt, A.M., Villanueva, A.R., Foldes, J., and Rao, D.S. 1995. Relations between histologic indices of bone formation: implications for the patho- genesis of spinal osteoporosis. J. Bone Miner. Res. 10:466-473. source
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [9] 9. Ebeling, P.R., et al. 1996. Bone turnover markers and bone density across the menopausal transi- tion. J. Clin. Endocrinol. Metab. 81:3366-3371.
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Treatment with COX inhibitors blunts the response to impact loading and fluid shear stress, indicating that prostaglandins play an important role in the response mechanical forces”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Cytokines, prostaglandins, NO, and leukotrienes
What the sources say
- Not checked — no full text of the sourcecites [90] 90. Forwood, M.R. 1996. Inducible cyclo-oxygenase (COX-2) mediates the induction of bone forma- tion by mechanical loading in vivo. J. Bone Miner. Res. 11:1688-1693. source
- Not checked — no full text of the sourcecites [91] 91. Bakker, A.D., et al. 2004. Additive effects of estro- gen and mechanical stress on nitric oxide and prostaglandin E(2) production by bone cells from osteoporotic donors. Osteoporos. Int. 16:983-989. source
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“One of these, raloxifene, has been shown to decrease the risk of vertebral fracture and does not appear to increase the risk of breast cancer (114).”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Implication for the diagnosis and treatment of osteoporosis
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [114]
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Data from the Women's Health Initiative indicated that the estrogen, particularly when combined with progestins, increased the risk of breast cancer and cardiovascular disease, which outweighed the benefits to the skeleton.”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Implication for the diagnosis and treatment of osteoporosis
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [113]
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Leukotrienes, the products of lipoxygenase, can affect bone by stimulating resorption and inhibiting formation”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Cytokines, prostaglandins, NO, and leukotrienes
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [97] 97. Traianedes, K., Dallas, M.R., Garrett, I.R., Mundy, G.R., and Bonewald, L.F. 1998. 5-Lipoxygenase metabolites inhibit bone formation in vitro. Endo- crinology. 139:3178-3184.
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“The clinical trials showing that bisphosphonates could provide effective and relatively safe antiresorptive therapy have had an enormous impact on the management of osteoporosis.”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Implication for the diagnosis and treatment of osteoporosis
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [112]
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [114]
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While improvements in diagnosis and therapy are important, it is equally true that we have sufficient tools today to assess fracture risk and prevent or treat osteoporosis to reduce that risk.”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Implication for the diagnosis and treatment of osteoporosis
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: The rate of bone remodeling is a key predictor of fracture risk.
- Rests on an assumption: Increased bone resorption and formation markers are associated with higher risk of bone loss and fragility fractures.
- Rests on an assumption: Genetic factors largely determine whether an individual reaches optimal peak bone mass.
- Rests on an assumption: Nutrition and lifestyle can affect peak bone mass during growth and development.
- Rests on an assumption: Calcium and vitamin D sufficiency and regular physical activity may raise peak bone mass, slow bone loss, and lower fracture risk over life.
None of the sources cited for this claim have been checked yet.
In the paper
“Some, but not all, epidemiologic studies suggest that β-adrenergic blockers can decrease fracture risk and increase BMD (106, 107).”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Leptin and neural pathways
What the sources say
- Not checked — no full text of the sourcecites [106] 106. Rodan, G.A., and Martin, T.J. 2000. Therapeutic approaches to bone diseases. Science. 289:1508-1514. source
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [107]
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Moreover, it is critical that we meet both these challenges in the coming decades if we are to deal effectively with the increase in osteoporosis and fractures that is projected as our population ages (111).”
§ Pathogenesis of osteoporosis: concepts, conflicts, and prospects > Implication for the diagnosis and treatment of osteoporosis
What the sources say
- Not matched
  Couldn’t be matched to a paper in Crossref, so it can’t be checked.
  cites [111]
Strength:plain· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.

33 of 33

The authors state this as an assumption.
The stromal/osteoblastic lineage is the main source of RANKL in normal bone remodeling.
“While it is assumed that cells of the stromal/osteoblastic lineage are the major source of RANKL in physiologic bone remodeling”
The paper relies on this without support.
Osteoporosis is a complex polygenic disorder.
“Since osteoporosis is a complex, polygenic disorder”
The paper relies on this without support.
Current knowledge about osteoporosis is not applied broadly in the community.
“The latter is far from being met.”
The paper relies on this without support.
The rate of bone remodeling is a key predictor of fracture risk.
“Another key predictor is the rate of bone remodeling.”
The paper relies on this without support.
Increased bone resorption and formation markers are associated with higher risk of bone loss and fragility fractures.
“Increased rates of osteoclastic bone resorption, measured by the level of collagen breakdown products, as well as increased bone formation, measured by bonespecific alkaline phosphatase, osteocalcin, or procollagen peptide levels, are associated with an increase in risk for bone loss and fragility fractures.”
The paper relies on this without support.
Genetic factors largely determine whether an individual reaches optimal peak bone mass.
“While the first major pathogenetic mechanism, failure to achieve optimal peak bone mass, is determined largely by our genes, nutrition and lifestyle can have an effect during growth and development.”
The paper relies on this without support.
Nutrition and lifestyle can affect peak bone mass during growth and development.
“While the first major pathogenetic mechanism, failure to achieve optimal peak bone mass, is determined largely by our genes, nutrition and lifestyle can have an effect during growth and development.”
The paper relies on this without support.
Calcium and vitamin D sufficiency and regular physical activity may raise peak bone mass, slow bone loss, and lower fracture risk over life.
“Moreover, adequate calcium and vitamin D intake and appropriate physical activity may not only increase peak bone mass but also slow bone loss and reduce fracture risk throughout life.”

8 of 8

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Self-check results appear here once an independent check has confirmed them.

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

Cites a retracted work: 10.1359/jbmr.040716
Info
The cited work was retracted; the date of the notice is not on record.
Cited work 10.1359/jbmr.040716 · retraction date not known · this paper published 2005-12-01

1 of 1

1 retracted

RETRACTION: Isosorbide Mononitrate Increases Bone Formation and Decreases Bone Resorption in Postmenopausal Women: A Randomized Trial
Jamal, S. A., Cummings, S. R., & HAWKER, G. A. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040716 · Cited by 86
Retracted
Effect of Parathyroid Hormone (1-34) on Fractures and Bone Mineral Density in Postmenopausal Women with Osteoporosis
Neer, R. M., Arnaud, C. D., Zanchetta, J. R., Prince, R., Gaich, G. A., Reginster, J.-Y., Hodsman, A. B., Eriksen, E. F., Ish-Shalom, S., Genant, H. K., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200105103441904 · Cited by 4,602
Effects of Conjugated Equine Estrogen in Postmenopausal Women With Hysterectomy: The Women's Health Initiative Randomized Controlled Trial
(2004) · JAMA · doi:10.1001/jama.291.14.1701 · Cited by 4,534
Osf2/Cbfa1: A Transcriptional Activator of Osteoblast Differentiation
Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997) · Cell · doi:10.1016/s0092-8674(00)80257-3 · Cited by 4,246
The Novel Zinc Finger-Containing Transcription Factor Osterix Is Required for Osteoblast Differentiation and Bone Formation
Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J. M., Behringer, R. R., & de Crombrugghe, B. (2002) · Cell · doi:10.1016/s0092-8674(01)00622-5 · Cited by 3,608
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483
Modulation of Osteoclast Differentiation and Function by the New Members of the Tumor Necrosis Factor Receptor and Ligand Families
Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M. T., & Martin, T. J. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0367 · Cited by 2,345
LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development
Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00571-2 · Cited by 2,235
Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications.
Lips, P. (2001) · Endocrine reviews · doi:10.1210/edrv.22.4.0437 · Cited by 2,203
Leptin Inhibits Bone Formation through a Hypothalamic Relay
Ducy, P., Amling, M., Takeda, S., Priemel, M., Schilling, A. F., Beil, F. T., Shen, J., Vinson, C., Rueger, J. M., & Karsenty, G. (2000) · Cell · doi:10.1016/s0092-8674(00)81558-5 · Cited by 2,077

Flagged first, then by citations

Show all 145 references

12 of the 145 references couldn’t be matched to a known paper.

Sorted by citations

Items 301–400 of 1,775

Parathyroid hormone‐related protein (107–139) increases human osteoblastic cell survival by activation of vascular endothelial growth factor receptor‐2
Alonso, V., Gortázar, A. R., Ardura, J. A., Andrade‐Zapata, I., Alvarez-Arroyo, M. V., & Esbrit, P. (2008) · Journal of Cellular Physiology · doi:10.1002/jcp.21547 · Cited by 59
“The pathogenesis of osteoporosis involves a relative deficit of bone formation to compensate the excessive bone resorption associated with increased bone remodeling units (Raisz, 2005).”
Background
Estradiol rapidly inhibits osteoclastogenesis and RANKL expression in bone marrow cultures in postmenopausal women: a pilot study
Taxel, P., Kaneko, H., Lee, S.-K., Aguila, H. L., Raisz, L. G., & Lorenzo, J. A. (2008) · Osteoporosis International · doi:10.1007/s00198-007-0452-7 · Cited by 58
“While it is well established that estrogen deficiency is a critical factor in the pathogenesis of osteoporosis, the precise mechanisms by which estrogen deficiency results in bone loss are still not clear [1, 2].”
BackgroundSelf-citation
Role of Curcumin in Common Musculoskeletal Disorders: a Review of Current Laboratory, Translational, and Clinical Data
Peddada, K. V., Peddada, K. V., Shukla, S. K., et al. (2015) · Orthopaedic Surgery · doi:10.1111/os.12183 · Cited by 58
Bioactivity‐guided Isolation of Antiosteoporotic Compounds from Ligustrum lucidum
Chen, Q., Yang, L., Zhang, G., et al. (2012) · Phytotherapy Research · doi:10.1002/ptr.4820 · Cited by 58
“Raisz LG. 2005.”
Estrogen therapy for postmenopausal osteoporosis
Fitzpatrick, L. A. (2006) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302006000400016 · Cited by 60
“Studies in transgenic mice that overproduce OPG, which blocks RANKL/RANK interactions, resulted in a skeletal phenotype consistent with osteopetrosis (10), while OPG knockout mice had a phenotype consistent with severe osteoporosis and a high incidence of fracture (11).”
Background
Cissus quadrangularis extract enhances biomineralization through up-regulation of MAPK-dependent alkaline phosphatase activity in osteoblasts
Parisuthiman, D., Singhatanadgit, W., Dechatiwongse, T., et al. (2008) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-008-9158-1 · Cited by 58
Calcium-phosphate-coated Oral Implants Promote Osseointegration in Osteoporosis
Alghamdi, H. S., Cuijpers, V. M. J. I., Wolke, J. G. C., et al. (2013) · Journal of Dental Research · doi:10.1177/0022034513505769 · Cited by 58
“Osteoporosis is characterized by a severe decrease in bone mineral density (BMD), resulting in reduced bone strength and alteration of trabecular bone characteristics (Raisz, 2005).”
Background
Clinical Efficacy on Fracture Risk and Safety of 0.5 mg or 1 mg/month Intravenous Ibandronate Versus 2.5 mg/day Oral Risedronate in Patients with Primary Osteoporosis
For the MOVER Study Group, Nakamura, T., Nakano, T., Ito, M., Hagino, H., Hashimoto, J., Tobinai, M., & Mizunuma, H. (2013) · Calcified Tissue International · doi:10.1007/s00223-013-9734-6 · Cited by 58
“Meta-analyses have shown that fracture risks of men and women are similar for any given BMD [23, 24]; thus postmenopausal osteoporosis and osteoporosis in elderly men can be categorized as primary osteoporosis with possible heterogeneous pathogenesis [25, 26].”
Background
The beneficial effect of Icaritin on osteoporotic bone is dependent on the treatment initiation timing in adult ovariectomized rats
Peng, S., Zhang, G., Zhang, B., et al. (2013) · Bone · doi:10.1016/j.bone.2013.02.012 · Cited by 58
Bone-Protective Effects of Dried Plum in Postmenopausal Women: Efficacy and Possible Mechanisms
Arjmandi, B. H., Johnson, S. A., Pourafshar, S., Navaei, N., George, K. S., Hooshmand, S., Chai, S. C., & Akhavan, N. S. (2017) · Nutrients · doi:10.3390/nu9050496 · Cited by 59
“Osteoporosis is a chronic and debilitating age-related skeletal disease characterized by the loss of bone mass and a deterioration of the microstructural properties of bone, resulting in an increased propensity for fragility fractures [4].”
Background
The Bone—Vasculature Axis: Calcium Supplementation and the Role of Vitamin K
Wasilewski, G. B., Vervloet, M. G., & Schurgers, L. J. (2019) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2019.00006 · Cited by 59
Bone Regeneration Associated with Nontherapeutic and Therapeutic Surface Coatings for Dental Implants in Osteoporosis
Alghamdi, H. S., & Jansen, J. A. (2012) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2012.0400 · Cited by 58
Selective targeting of RANK signaling pathways as new therapeutic strategies for osteoporosis
Jules, J., Ashley, J. W., & Feng, X. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2010.511179 · Cited by 58
“However, when its formation, activity and/or survival is aberrantly elevated, the osteoclast can play a role in the pathogenesis of a variety of bone disorders including osteoporosis [6,7], bone erosion in inflammatory conditions [8,9] and tumor-induced osteolysis [10].”
Background
Ferutinin directs dental pulp-derived stem cells towards the osteogenic lineage by epigenetically regulating canonical Wnt signaling
Rolph, D. N., Deb, M., Kanji, S., Greene, C. J., Das, M., Joseph, M., Aggarwal, R., Leblebicioğlu, B., & Das, H. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.10.032 · Cited by 54
“Osteoporosis results from excessive resorption by osteoclasts coupled with inadequate osteoblast activity that is insufficient to properly restore bone [18], leading to structural alterations and reduction in BMD.”
Background
Eurycoma longifolia : Medicinal Plant in the Prevention and Treatment of Male Osteoporosis due to Androgen Deficiency
Mohd Effendy, N., Mohamed, N., Muhammad, N., Naina Mohamad, I., & Shuid, A. N. (2012) · Evidence-Based Complementary and Alternative Medicine · doi:10.1155/2012/125761 · Cited by 55
“Therefore, any factors that increase the rate of bone remodelling, such as hormonal deficiency, will result in loss of bone mass [40].”
Background
Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells
Biçer, M., Cottrell, G. S., & Widera, D. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-02094-8 · Cited by 58
“uk (1)Stem Cell Biology and Regenerative Medicine Group, Reading School of Pharmacy, University of Reading, PO Box 226, Whiteknights, Reading RG6 6AP, UK Full list of author information is available at the end of the article Osteoporosis is characterised by low bone mass which is strongly associated with increased bon…”
Background
Should bisphosphonates be used for long‐term treatment of glucocorticoid‐induced osteoporosis?
Teitelbaum, S. L., Seton, M., & Saag, K. G. (2010) · Arthritis & Rheumatism · doi:10.1002/art.30135 · Cited by 54
“When the activity of osteoclasts supersedes that of osteoblasts, bone loss occurs, which, if profound, eventuates into osteoporosis (1).”
Recovery Of Bone And Muscle Mass In Patients With Chronic Kidney Disease And Iron Overload On Hemodialysis And Taking Combined Supplementation With Curcumin And Resveratrol
Murillo-Ortiz, B. O., Preciado, A. R. F., Ramı́rez-Emiliano, J., Martı́nez-Garza, S., Ramos-Rodríguez, E., & Macías, L. A. D. A. (2019) · Clinical Interventions in Aging · doi:10.2147/cia.s223805 · Cited by 55
“In subjects with osteopenia, this balance is affected by excessive bone resorption or inadequate bone formation during bone remodeling, resulting in low bone density.(5,6) Iron overload is a common complication in patients with CKD in hemodialysis; it results from the transfusions of red cells that these patients rece…”
Background
Meta-Analysis Reveals Compositional and Functional Microbial Changes Associated with Osteoporosis
Akinsuyi, O., & Roesch, L. F. W. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.00322-23 · Cited by 55
Estrogen receptor α36 mediates a bone-sparing effect of 17β-estrodiol in postmenopausal women
Xie, H., Sun, M., Liao, X., Yuan, L., Sheng, Z., Meng, J.-C., Wang, D., Yu, Z., Zhang, L., Zhou, H., et al. (2010) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.169 · Cited by 53
“(28,29) Here we found that OBs and OCs from normal postmenopausal women express high levels of endogenous ER-a36 and response to E2 at a concentration of 10 pM (a postmenopausal level of E2).”
Background
Progression of aortic valve stenosis is associated with bone remodelling and secondary hyperparathyroidism in elderly patients—the COFRASA study
Hekimian, G., Boutten, A., Flamant, M., Duval, X., Dehoux, M., Benessiano, J., Huart, V., Dupré, T., Berjeb, N., Tubach, F., et al. (2013) · European Heart Journal · doi:10.1093/eurheartj/ehs450 · Cited by 53
Treatment of bone disorders in liver disease
Parés, A., & Guañabens, N. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2006.06.007 · Cited by 50
“Osteoporosis is highly prevalent in patients with liver disease, and it is characterized by loss of bone mass and strength that leads to fragility fractures [1].”
Background
The Dual Faces of Oestrogen: The Impact of Exogenous Oestrogen on the Physiological and Pathophysiological Functions of Tissues and Organs
Bartkowiak-Wieczorek, J., Jaros, A., Gajdzińska, A., Wojtyła-Buciora, P., Szymański, I., Szymaniak, J., Janusz, W., Walczak, I., Jonaszka, G., & Bienert, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158167 · Cited by 63
“Albright [42] observed that oestrogen deficiency is the cause of postmenopausal osteoporosis.”
Background
Deficiency of ATP6V1H Causes Bone Loss by Inhibiting Bone Resorption and Bone Formation through the TGF-β1 Pathway
Duan, X., Liu, J., Zheng, X., Wang, Z., Zhang, Y., Hao, Y., Yang, T., & Deng, H. (2016) · Theranostics · doi:10.7150/thno.17140 · Cited by 52
“Several genes are known to influence bone mass, including the vitamin D receptor, estrogen receptor, and collagen type I alpha I gene [19, 20].”
Background
Monoclonal antibodies for treating osteoporosis
Faienza, M. F., Chiarito, M., D’Amato, G., Colaianni, G., Colucci, S. C., Grano, M., & Brunetti, G. (2017) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1401607 · Cited by 52
“quantity of bone resorbed by OCs exceeds the amounts deposed by OBs consequently damaging the skeletal architecture and decreasing bone strength [8].”
Background
Effects of Type 2 Diabetic Serum on Proliferation and Osteogenic Differentiation of Mesenchymal Stem Cells
Deng, X., Xu, M., Shen, M., & Cheng, J. (2018) · Journal of Diabetes Research · doi:10.1155/2018/5765478 · Cited by 55
The Roadmap of RANKL/RANK Pathway in Cancer
Casimiro, S., Vilhais, G., Gomes, I., & Costa, L. (2021) · Cells · doi:10.3390/cells10081978 · Cited by 55
“Estrogen is a known regulator of bone physiology and pathophysiology and has been shown to protect bone by regulating osteoclast survival, either by inducing autocrine TGF-β expression or by upregulating the apoptosis-promoting Fas ligand in osteoblasts [69,70].”
Background
Ex vivo Bone Models and Their Potential in Preclinical Evaluation
Cramer, E. E. A., Ito, K., & Hofmann, S. (2021) · Current Osteoporosis Reports · doi:10.1007/s11914-020-00649-5 · Cited by 53
A Calcium-Collagen Chelate Dietary Supplement Attenuates Bone Loss in Postmenopausal Women with Osteopenia: A Randomized Controlled Trial
Elam, M. L., Johnson, S. A., Hooshmand, S., Feresin, R. G., Payton, M. E., Gu, J. L., & Arjmandi, B. H. (2014) · Journal of Medicinal Food · doi:10.1089/jmf.2014.0100 · Cited by 55
“O steoporosis is a chronic and potentially debilitating condition characterized by decreased bone mass and quality resulting in an increased tendency to develop fragility fractures.(1) In the United States alone, more than 44 million people either have or are at risk of osteoporosis.”
MiR-21 overexpression improves osteoporosis by targeting RECK
Zhao, W., Dong, Y., Wu, C., Ma, Y., Jin, Y., & Ji, Y. (2015) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-015-2404-4 · Cited by 55
Osteoblast ontogeny and implications for bone pathology: an overview
Titorencu, I. D., Prună, V., Jinga, V. V., & Simionescu, M. (2013) · Cell and Tissue Research · doi:10.1007/s00441-013-1750-3 · Cited by 55
“Osteoporosis This disease is the result of several pathogenic mechanisms converging in the loss of bone mass and density and an alteration in bone strength and architecture.”
Background
Successful Spinal Fusion by E. coli-derived BMP-2-adsorbed Porous β-TCP Granules: A Pilot Study
Dohzono, S., Imai, Y., Nakamura, H., Wakitani, S., & Takaoka, K. (2009) · Clinical Orthopaedics and Related Research · doi:10.1007/s11999-009-0960-1 · Cited by 53
“This excessive osteoclast differentiation and bone resorption is an indirect effect of osteoblast differentiation and RANKL (receptor activator of NFjB ligand) expression induced by BMP stimulation [ 28 , 37, 46] and a direct effect of BMP on osteoclastogenesis [44].”
Background
Solid-State Quantitative 1H and 31P MRI of Cortical Bone in Humans
Seifert, A. C., & Wehrli, F. W. (2016) · Current Osteoporosis Reports · doi:10.1007/s11914-016-0307-2 · Cited by 52
Anti-osteoporotic effects of syringic acid and vanilic acid in the extracts of waste beds after mushroom cultivation
Tanaka, T., Onuma, H., Shigihara, T., et al. (2019) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2019.04.021 · Cited by 52
A review on osteoclast diseases and osteoclastogenesis inhibitors recently developed from natural resources
Wang, X., Yamauchi, K., & Mitsunaga, T. (2020) · Fitoterapia · doi:10.1016/j.fitote.2020.104482 · Cited by 54
Arctiin abrogates osteoclastogenesis and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation
Chen, D., Ye, Z., Wang, C., Wang, Q., Wang, H., Kuek, V., Wang, Z., Qiu, H., Yuan, J., Kenny, J., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104944 · Cited by 54
Strontium fructose 1,6-diphosphate prevents bone loss in a rat model of postmenopausal osteoporosis via the OPG/RANKL/RANK pathway
Ma, B., Zhang, Q., Wu, D., Wang, Y., Hu, Y., Cheng, Y.-P., Yang, Z.-D., Zheng, Y.-Y., & Ying, H. (2012) · Acta Pharmacologica Sinica · doi:10.1038/aps.2011.177 · Cited by 51
Low-Bone-Mass Phenotype of Deficient Mice for the Cluster of Differentiation 36 (CD36)
Kevorkova, O., Martineau, C., Falstrault, L., Sanchez-Dardon, J. L., Brissette, L., & Moreau, R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077701 · Cited by 51
“Any imbalance between the functions of resorptive and formative cell populations that leads to excessive bone resorption or inadequate formation response results in loss of bone density, lower bone mass and increased risk of bone fractures [3] which are the main diagnostic criteria of osteoporosis [4].”
Background
Serum response factor regulates bone formation via IGF-1 and Runx2 signals
Chen, J., Yuan, K., Mao, X., Miano, J. M., Wu, H., & Chen, Y. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1607 · Cited by 51
“Insulin-like growth factors (IGFs) are important growth factors for the acquisition of bone mass during adolescence and maintenance of bone remodeling during adult life.((1,4,8)) These secreted factors and related signaling pathways either promote or suppress the expression and/or function of transcription factors ess…”
Background
The diagnostic value of microscopy in dry bone palaeopathology: A review
de Boer, H. H., van der Merwe, A. E., & Maat, G. J. R. (2013) · International Journal of Paleopathology · doi:10.1016/j.ijpp.2013.03.004 · Cited by 51
An open, prospective, non‐randomized, controlled, multicentre study to evaluate the clinical outcome of implant treatment in women over 60 years of age with osteoporosis/osteopenia: 1‐year results
Temmerman, A., Rasmusson, L., Kübler, A. C., Thor, A. L. I., & Quirynen, M. (2016) · Clinical Oral Implants Research · doi:10.1111/clr.12766 · Cited by 51
IL-17 promotes osteoblast differentiation, bone regeneration, and remodeling in mice
Kim, H. J., Seo, S. J., Kim, J., Kim, Y., & Lee, Y. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.02.054 · Cited by 54
Red Light-Mediated Photoredox Catalysis Triggers Nitric Oxide Release for Treatment of Cutibacterium Acne Induced Intervertebral Disc Degeneration
Tao, S., Shen, Z., Chen, J., Shan, Z., Huang, B. H., Zhang, X., Zheng, L., Liu, J., You, T., Zhao, F., et al. (2022) · ACS Nano · doi:10.1021/acsnano.2c06328 · Cited by 50
Increased circulating heat shock protein 60 induced by menopause, stimulates apoptosis of osteoblast-lineage cells via up-regulation of toll-like receptors
Kim, Y. S., Koh, J., Lee, Y., Kim, B., Lee, S. H., Lee, K., & Kim, G. S. (2009) · Bone · doi:10.1016/j.bone.2009.03.658 · Cited by 50
“Estrogen also acts indirectly on osteoblast lineages via local mediators [12], such as cytokines and growth factors, derived from osteoclast lineages and T-lymphocytes [13,14].”
Background
Sphingosin 1-phosphate contributes in tumor progression
Samadi, N., Tabasinezhad, M., Ghanbari, P., Mohseni, M. M., Saei, A. A., Sharifi, S., Saeedi, N., & Pourhassan, A. (2013) · Journal of Cancer Research and Therapeutics · doi:10.4103/0973-1482.126446 · Cited by 50
Puerarin Exerted Anti-Osteoporotic Action Independent of Estrogen Receptor-Mediated Pathway
Michihara, S., Tanaka, T., Uzawa, Y., Moriyama, T., & Kawamura, Y. (2012) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.58.202 · Cited by 50
Bone and Mineral Metabolism
Risteli, J., Winter, W. E., Kleerekoper, M., & Risteli, L. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4160-6164-9.00052-4 · Cited by 52
In Situ Self‐Assembling Micellar Depots that Can Actively Trap and Passively Release NO with Long‐Lasting Activity to Reverse Osteoporosis
Lin, Y., Chen, C., Chi, N., Nguyen, T. H. M., Lu, H., Nguyen, D., Lai, P., & Sung, H. (2018) · Advanced Materials · doi:10.1002/adma.201705605 · Cited by 50
Sustained release of vitamin C from PCL coated TCP induces proliferation and differentiation of osteoblast cells and suppresses osteosarcoma cell growth
Bose, S., Sarkar, N., & Vahabzadeh, S. (2019) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.110096 · Cited by 49
Changes to Osteoporosis Prevalence According to Method of Risk Assessment
Richards, J. B., Leslie, W. D., Joseph, L., et al. (2006) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.061109 · Cited by 50
“OSTEOPOROSIS IS A disease characterized by an increased propensity to fracture caused by a loss of bone strength.((1)) In 1994, the World Health Organization (WHO) set the criterion for diagnosing osteoporosis in white women as a BMD 2.”
Background
Bone Physiology, Disease and Treatment
Post, T. M., Cremers, S. C. L. M., Kerbusch, T., & Danhof, M. (2010) · Clinical Pharmacokinetics · doi:10.2165/11318150-000000000-00000 · Cited by 52
Calcium Supplement by Tetracycline guided amorphous Calcium Carbonate potentiates Osteoblast promotion for Synergetic Osteoporosis Therapy
Wang, J., Tao, S., Jin, X., Song, Y., Zhou, W., Lou, H.-Y., Zhao, R., Wang, C., Hu, F., & Yuan, H. (2020) · Theranostics · doi:10.7150/thno.45142 · Cited by 49
“However, this approach usually requires relatively large dosage of calcium supplement and suffered from poor outcome which might due the fact that most of the adopted calcium ions are excreted without precise targeting to the lesions [6].”
Background
Estrogen Inhibits RANKL-Induced Osteoclastic Differentiation by Increasing the Expression of TRPV5 Channel
Chen, F., Ouyang, Y., Ye, T., Ni, B., & Chen, A. (2013) · Journal of Cellular Biochemistry · doi:10.1002/jcb.24700 · Cited by 51
Association between osteoporosis and psoriasis: results from the Longitudinal Health Insurance Database in Taiwan
Keller, J. J., Kang, J., & Lin, H. (2012) · Osteoporosis International · doi:10.1007/s00198-012-2185-5 · Cited by 49
Do polyunsaturated fatty acids protect against bone loss in our aging and osteoporotic population?
Martyniak, K., Wei, F., Ballesteros, A., Meckmongkol, T. T., Calder, A. N., Gilbertson, T. A., Orlovskaya, N. A., & Coathup, M. J. (2020) · Bone · doi:10.1016/j.bone.2020.115736 · Cited by 52
Fibrin Accumulation Secondary to Loss of Plasmin‐Mediated Fibrinolysis Drives Inflammatory Osteoporosis in Mice
Cole, H., Ohba, T., Nyman, J. S., Haro, H., Cates, J., Flick, M. J., Degen, J. L., & Schoenecker, J. G. (2014) · Arthritis & Rheumatology · doi:10.1002/art.38639 · Cited by 48
The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice
Vinik, Y., Shatz‐Azoulay, H., Vivanti, A., Hever, N., Levy, Y. A., Karmona, R., Brumfeld, V., Baraghithy, S., Attar-Lamdar, M., Boura‐Halfon, S., et al. (2015) · eLife · doi:10.7554/elife.05914 · Cited by 47
“In that 321 respect, our model of Tg mice resembles in certain aspects the changes in bone turnover that take 322 place during postmenopausal osteoporosis (Raisz 2005; Feng and McDonald 2011).”
BackgroundResultInfluential
Estrogen augments shear stress–induced signaling and gene expression in osteoblast-like cells via estrogen receptor–mediated expression of β1-integrin
Yeh, C.-R., Chiu, J., Lee, C.-I., Lee, P.-L., Shih, Y., Sun, J., Chien, S., & Cheng, C. (2009) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.091008 · Cited by 47
“A deficiency of estrogen accelerates bone lose; this is probably the major reason leading to osteoporosis in menopausal women.((9)) 17bEstradiol represents a major estrogen in human, and it is produced by granulose cells of the ovary, with small amounts also being produced by the adrenal cortex.”
Background
NOFSA Guideline for the Diagnosis and Management of Osteoporosis
Hough, S. F., Ascott-Evans, B. H., Brown, S. L., Cassim, B., de Villiers, T. J., Lipschitz, S., Pettifor, J. M., & Sonnendecker, E. W. W. (2010) · Journal of Endocrinology Metabolism and Diabetes of South Africa · doi:10.1080/22201009.2010.10872239 · Cited by 48
Correlation between bone mineral density and serum trace elements in response to supervised aerobic training in older adults
Gabr, S. A., Al-Ghadir, M., Alghadir, A. H., & Al-Eisa, E. S. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s100566 · Cited by 49
“This may be due to a reduction in bone mineral content, particularly of the hip.(17,18) Many research studies reported that osteoporosis, skeletal abnormalities, and inhibition of boner growth are linked with deficiency in Cu as shown in Menkin’s disease,(19) manganese as reported in chondrodystrophy,(20) and zinc as…”
Cryopreserved human bone marrow mononuclear cells as a source of mesenchymal stromal cells: application in osteoporosis research
Casado‐Díaz, A., Santiago‐Mora, R., Jiménez, R., Caballero‐Villarraso, J., Herrera, C., Torres, A., Dorado, G., & Quesada‐Gómez, J. M. (2008) · Cytotherapy · doi:10.1080/14653240802192644 · Cited by 48
Evaluation of bone mineral density in Turkish children with severe haemophilia A: Ankara hospital experience
Alioğlu, B., Selver, B., Özsoy, H., et al. (2011) · Haemophilia · doi:10.1111/j.1365-2516.2011.02587.x · Cited by 47
Regulation of the osteogenic and adipogenic differentiation of bone marrow-derived stromal cells by extracellular uridine triphosphate: The role of P2Y2 receptor and ERK1/2 signaling
Li, W., Wei, S., Liu, C., et al. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2400 · Cited by 47
“Osteoporosis is a systemic disease characterized by low bone mass, increased bone fragility and susceptibility to fracture (1).”
Efficiency of high molecular weight backbone degradable HPMA copolymer–Prostaglandin E1 conjugate in promotion of bone formation in ovariectomized rats
Pan, H., Sima, M., Miller, S. C., et al. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.05.003 · Cited by 47
“Such conjugates have a potential as therapeutics for the treatment of osteoporosis [21].”
Role of fibroblast growth factor 2 and wnt signaling in anabolic effects of parathyroid hormone on bone formation
Fei, Y., & Hurley, M. M. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.24075 · Cited by 46
Tryptophan Hydroxylase 1 (Tph-1)-Targeted Bone Anabolic Agents for Osteoporosis
Fu, H., Zhou, Y., Bao, B., Jia, M.-X., Zhao, Y., Zhang, L., Li, J., He, H., & Zhou, X. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5002293 · Cited by 48
miRNAs Related to Skeletal Diseases
Seeliger, C., Balmayor, E. R., & van Griensven, M. (2016) · Stem Cells and Development · doi:10.1089/scd.2016.0133 · Cited by 47
“Skeletal fragility is caused by excessive bone resorption, inadequate formation response during the bone remodeling or inefﬁcacy to produce the optimal bone mass [19]. miRNAs may have a crucial impact on these metabolic mechanisms.”
Osteoactivin inhibition of osteoclastogenesis is mediated through CD44-ERK signaling
Sondag, G. R., Mbimba, T., Moussa, F. M., Novak, K. M., Yu, B., Jaber, F. A., Abdelmagid, S. M., Geldenhuys, W. J., & Safadi, F. F. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.78 · Cited by 48
Computer-aided diagnosis systems for osteoporosis detection: a comprehensive survey
Wani, I. M., & Arora, S. (2020) · Medical & Biological Engineering & Computing · doi:10.1007/s11517-020-02171-3 · Cited by 52
Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial
Shen, C.-L., Yang, S., Tomison, M. D., Romero, A. W., Felton, C. K., & Mo, H. (2018) · Osteoporosis International · doi:10.1007/s00198-017-4356-x · Cited by 46
“(osteoclasts) and bone formation (osteoblasts) activities [34].”
Bovine milk extracellular vesicles induce the proliferation and differentiation of osteoblasts and promote osteogenesis in rats
Go, G., Jeon, J., Lee, G., Lee, J. H., & Lee, S. H. (2021) · Journal of Food Biochemistry · doi:10.1111/jfbc.13705 · Cited by 46
“However, due to various causes, if the activity of the osteoblasts decrease or the activity of the osteoclasts increase, this balance is destroyed and bone diseases such as osteoporosis occur (Raisz, 2005).”
Background
The effects of untreated and treated HIV infection on bone disease
Cotter, A. G., & Mallon, P. W. G. (2013) · Current Opinion in HIV and AIDS · doi:10.1097/coh.0000000000000028 · Cited by 48
“The lifespan of a single BMU is approximately 9 months with formation lagging behind resorption both in time and space, ensuring that any increases in bone turnover result in net reductions in BMD during what is termed a ‘catabolic window’ [6].”
Background
Anti-osteoclastogenic activity of matairesinol via suppression of p38/ERK-NFATc1 signaling axis
Choi, S., Park, K., Yeon, J., Ryu, B. J., Kim, K., & Kim, S. H. (2014) · BMC Complementary and Alternative Medicine · doi:10.1186/1472-6882-14-35 · Cited by 47
“Intervention in osteoclast differentiation and its function has been postulated as a treatment for bone metabolic diseases such as osteoporosis [15].”
Background
Tanshinone IIA blocks dexamethasone-induced apoptosis in osteoblasts through inhibiting Nox4-derived ROS production.
Li, J., He, C., Tong, W., Zou, Y., Li, D., Zhang, C., & Xu, W. (2015) · PubMed Central · Cited by 46
Osteoblast Role in Rheumatic Diseases
Corrado, A., Maruotti, N., & Cantatore, F. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061272 · Cited by 41
“Osteoporosis is a disorder characterized by an imbalance of bone turnover, resulting in a reduced bone mineral density, alteration of bone microarchitecture and an increased risk of fracture [92].”
Background
Apolipoprotein E plays crucial roles in maintaining bone mass by promoting osteoblast differentiation via ERK1/2 pathway and by suppressing osteoclast differentiation via c-Fos, NFATc1, and NF-κB pathway
Noguchi, T., Ebina, K., Hirao, M., Otsuru, S., Guess, A. J., Kawase, R., Ohama, T., Yamashita, S., Etani, Y., Okamura, G., et al. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.06.055 · Cited by 48
Ovariectomy/Orchiectomy in Rodents
Sophocleous, A., & Idris, A. I. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-8997-3_13 · Cited by 50
Learning from Monocyte-Macrophage Fusion and Multinucleation: Potential Therapeutic Targets for Osteoporosis and Rheumatoid Arthritis
Gambari, L., Grassi, F., Roseti, L., Grigolo, B., & Desando, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176001 · Cited by 46
“The uncoupling of bone resorption and bone formation (Figure 2) is the primary pathogenetic process in OP [89,90].”
Background
ERR receptors as potential targets in osteoporosis
Gallet, M., & Vanacker, J.-M. (2010) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2010.06.008 · Cited by 46
Probiotics as a New Regulator for Bone Health: A Systematic Review and Meta-Analysis
Malmir, H., Ejtahed, H., Soroush, A., Mortazavian, A. M., Fahimfar, N., Ostovar, A., Esmaillzadeh, A., Larijani, B. A., & Hasani‐Ranjbar, S. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/3582989 · Cited by 49
Characterizations and the Mechanism Underlying Osteogenic Activity of Peptides from Enzymatic Hydrolysates of Stichopus japonicus
Yang, M., Xu, Z., Wu, D., Dong, Y., Wang, Z., & Du, M. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c06028 · Cited by 46
Stimulative Effect of Ginsenosides Rg5:Rk1 on Murine Osteoblastic MC3T3‐E1 Cells
Siddiqi, M. H., Ṣiddiqi, M. Z., Ahn, S., et al. (2014) · Phytotherapy Research · doi:10.1002/ptr.5146 · Cited by 45
“…Korean Ginseng Center for Most roducts and Ginseng Resource Bank, Kyung Hee University, 9-701, Korea. yang@khu.ac.kr © 2014 John Wiley & Sons, Ltd. skeletal disorders, including osteoporosis (Huang et al., 2007; Kogianni and Noble, 2007; Parfitt, 1987; Raisz, 2005; Rodan, 1992; Teitelbaum, 2000).”
Induction of osteopenia during experimental tooth movement in the rat: alveolar bone remodelling and the mechanostat theory
Milne, T. J., Ichim, I., Patel, B., et al. (2009) · European Journal of Orthodontics · doi:10.1093/ejo/cjp032 · Cited by 45
Loss of Gsα in the Postnatal Skeleton Leads to Low Bone Mass and a Blunted Response to Anabolic Parathyroid Hormone Therapy
Sinha, P. S., Aarnisalo, P., Chubb, R., Poulton, I. J., Guo, J., Nachtrab, G. T., Kimura, T., Swami, S., Saeed, H., Chen, M., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.679753 · Cited by 44
In Situ Sensor Advancements for Osteoporosis Prevention, Diagnosis, and Treatment
Liu, L., & Webster, T. J. (2016) · Current Osteoporosis Reports · doi:10.1007/s11914-016-0339-7 · Cited by 44
“bone resorption occurs at a greater rate than bone formation, the bone loses density and puts people at risk of osteoporosis [23, 24].”
Background
Transplantation of Hepatocyte Growth Factor–Modified Dental Pulp Stem Cells Prevents Bone Loss in the Early Phase of Ovariectomy-Induced Osteoporosis
Kong, F., Shi, X., Xiao, F., Yang, Y., Zhang, X., Wang, L., Wu, C.-T., & Wang, H. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.091 · Cited by 45
“1,2 Worldwide, it causes > 8.9 million fractures annually, resulting in an osteoporotic fracture every 3 s. 3,4 The pathogenesis of osteoporosis stems from an improper balance between the processes of bone formation, achieved by the osteoid-secreting osteoblast, and bone resorption, carried out by…”
Influential
REV‐ERB agonism suppresses osteoclastogenesis and prevents ovariectomy‐induced bone loss partially via FABP4 upregulation
Song, C., Tan, P., Zhang, Z., Wu, W., Dong, Y., Zhao, L., Liu, H., Guan, H., & Li, F. (2018) · The FASEB Journal · doi:10.1096/fj.201600825rrr · Cited by 45
“precursors and function as the only bone resorptive cells (1).”
Background
Long lasting in-situ forming implant loaded with raloxifene HCl: An injectable delivery system for treatment of bone injuries
ElKasabgy, N. A., Abdel-Salam, F. S., Mahmoud, A. A. K., Basalious, E. B., Amer, M., Mostafa, A., & Elkheshen, S. A. (2019) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2019.118703 · Cited by 46
Rutin nanosuspension for potential management of osteoporosis: effect of particle size reduction on oral bioavailability, in vitro and in vivo activity
Gera, S., Pooladanda, V., Godugu, C., Challa, V. S., Wankar, J., Dodoala, S., & Sampathi, S. (2020) · Pharmaceutical Development and Technology · doi:10.1080/10837450.2020.1765378 · Cited by 46
An Enhancer 20 Kilobases Upstream of the Human Receptor Activator of Nuclear Factor-κB Ligand Gene Mediates Dominant Activation by 1,25-Dihydroxyvitamin D3
Nerenz, R. D., Martowicz, M. L., & Pike, J. W. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0380 · Cited by 45
Thiol-Functionalized, Antioxidant, and Osteogenic Mesoporous Silica Nanoparticles for Osteoporosis
Rasool, N., Negi, D., & Singh, Y. (2023) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.3c00479 · Cited by 45
The association between homocysteine (hcy) and serum natural antioxidants in elderly bone mineral densitometry (BMD)
Kuyumcu, M. E., Yeşil, Y., Öztürk, Z. A., Çınar, E., Kızılarslanoğlu, M. C., Halil, M. G., Ülger, Z., Yeşil, N. K., Cankurtaran, M., & Arıoğul, S. (2012) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2012.05.004 · Cited by 44
Prevalence and Characteristics of Bone Disease in Cirrhotic Patients Under Evaluation for Liver Transplantation
Vargas, A. A., Acevedo, J. M. P., Domingo, I. G., Jiménez, R. G., Martín, J. M. S., Ferrer, M. T., Mota, M. S., Gallego, Á. G., & Gómez‐Bravo, M. Á. (2012) · Transplantation Proceedings · doi:10.1016/j.transproceed.2012.05.011 · Cited by 43
From Stem Cells to Bone: Phenotype Acquisition, Stabilization, and Tissue Engineering in Animal Models
Gordeladze, J. O., Reseland, J. E., Duroux-Richard, I., Apparailly, F., & Jørgensen, C. (2010) · ILAR Journal · doi:10.1093/ilar.51.1.42 · Cited by 45
“…the loss of bone in patients with osteoporosis or in estrogen-defi cient osteoporotic animal models, we look at the theoretical consensus of how to build bone to reverse osteoporosis and repair microfractures (Glass and Karsenty 2007; Khosla et al. 2008; Manolagas and Almeida 2007; Raisz 2005).”
Background
Pathophysiology and clinical manifestations of osteoporosis
Becker, C. (2006) · Clinical cornerstone · doi:10.1016/s1098-3597(06)80062-1 · Cited by 45
Deletion of Orai1 alters expression of multiple genes during osteoclast and osteoblast maturation
Hwang, S., Foley, J. F., Numaga‐Tomita, T., Petranka, J. G., Bird, G. S. J., & Putney, J. W. (2012) · Cell Calcium · doi:10.1016/j.ceca.2012.10.001 · Cited by 45
Inhibition of BMP2-Induced Bone Formation by the p65 Subunit of NF-κB via an Interaction With Smad4
Hirata‐Tsuchiya, S., Fukushima, H., Katagiri, T., Ohte, S., Shin, M., Nagano, K., Aoki, K., Morotomi, T., Sugiyama, G., Nakatomi, C., et al. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1094 · Cited by 44
Akt drives buffalo casein-derived novel peptide-mediated osteoblast differentiation
Reddi, S., Kumar, N., Vij, R., Mada, S. B., Kapila, S., & Kapila, R. (2016) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2016.08.003 · Cited by 43
miR-375-3p negatively regulates osteogenesis by targeting and decreasing the expression levels of LRP5 and β-catenin
Sun, T., Li, C., Xiong, L., Ning, Z., Leung, F. K. L., Peng, S., & Lu, W. W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0171281 · Cited by 44
Connective Tissue and Age-Related Diseases
Sarbacher, C. A., & Halper, J. T. (2019) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-3681-2_11 · Cited by 43

Authors: Raisz, L. G.
Affiliations: UConn Health (US)
Corresponding author: Raisz, L. G.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2005-12-01
Volume: 115
Issue: 12
Pages: 3318-3325
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci27071
PMC: PMC1297264
OpenAlex: W2069811152
Cited by: 1,779
References: 145
Citations by year: 2026: 49 · 2025: 69 · 2024: 80 · 2023: 70 · 2022: 79 · 2021: 94 · 2020: 79 · 2019: 80 · 2018: 93 · 2017: 108 · 2016: 101 · 2015: 92 · 2014: 103 · 2013: 110 · 2012: 108
FWCI: 11.33
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
Keywords: osteoporosis pathogenesis, bone fragility, bone resorption, bone formation, estrogen deficiency, calcium deficiency, vitamin D deficiency, secondary hyperparathyroidism, bone remodeling, osteoblasts, osteoclasts, bone marrow cells, cytokines, growth factors, transcription factors, genetic polymorphism, bone mass, fracture risk, antiresorptive therapy
MeSH terms: Animals, Bone and Bones, Calcium, Cell Differentiation, Collagen, Estrogens, Glycoproteins, Hematopoietic Stem Cells, Hormones, Humans, Ligands, Models, Biological, Neurons, Nitric Oxide, Osteoblasts, Osteoporosis, Parathyroid Hormone, Prostaglandins, Vitamin D, Vitamin D Deficiency, Bone Density, Osteoporosis, Postmenopausal, NF-kappa B, Bone Remodeling, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Leptin, Fractures, Bone, Mice, Osteoprotegerin

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-09-30, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-09-30 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Pathogenesis of osteoporosis: concepts, conflicts, and prospects

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Self-check

Cited works that were retracted

Citations

Cites

Cited by

Related

Metadata

Record

About these checks