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

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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.

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Crossref · 10.1172/jci27071

Cites

133 of 133 references verified0 citation errors · 0 not checkable

Statistics

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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
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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
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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
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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
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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
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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
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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
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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

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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

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Items 401–500 of 1,775

Absence of ERRα in Female Mice Confers Resistance to Bone Loss Induced by Age or Estrogen-Deficiency
Teyssier, C., Gallet, M., Rabier, B., Monfoulet, L., Dine, J., Macari, C., Espallergues, J., Horard, B., Giguère, V., Cohen-Solal, M. E., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007942 · Cited by 44
“This is particularly illustrated after menopause in aging women, when the fall of circulating level of estrogens leads to enhanced bone remodeling with an excessive resorption [10,11].”
Background
Increased prevalence of vitamin D insufficiency in patients with breast cancer after neoadjuvant chemotherapy
Jacot, W., Pouderoux, S., Thézenas, S., Chapelle, A., Bleuse, J., Romieu, G., & Lamy, P. (2012) · Breast Cancer Research and Treatment · doi:10.1007/s10549-012-2084-7 · Cited by 44
“within the bone matrix [45, 46].”
Microelement strontium and human health: comprehensive analysis of the role in inflammation and non-communicable diseases (NCDs)
Ru, X., Yang, L., Shen, G., Wang, K., Xu, Z., Bian, W., Zhu, W., & Guo, Y. (2024) · Frontiers in Chemistry · doi:10.3389/fchem.2024.1367395 · Cited by 51
“Studies have demonstrated that Sr in ﬂ uences bone turnover, marked by simultaneous increases in bone formation and bone resorption (Raisz, 2005; Seeman and Delmas, 2006; Mentaverri et al., 2012).”
Background
Overexpression of integrin a2 promotes osteogenic differentiation of hBMSCs from senile osteoporosis through the ERK pathway.
Hu, H., Liu, Y., Wang, Z., Liu, Y., Fan, J., Fan, J., Liu, J., & Luo, Z. (2013) · Europe PMC (PubMed Central) · Cited by 43
Ginsenoside-Rb2 Inhibits Dexamethasone-Induced Apoptosis Through Promotion of GPR120 Induction in Bone Marrow-Derived Mesenchymal Stem Cells
Gao, B., Huang, Q., Jie, Q., Zhang, H., Wang, L., Guo, Y., Sun, Z., Wei, B.-Y., Han, Y., Liu, J., et al. (2014) · Stem Cells and Development · doi:10.1089/scd.2014.0367 · Cited by 43
Osteoblast differentiation and survival: A role for A2B adenosine receptor allosteric modulators
Trincavelli, M. L., Daniele, S., Giacomelli, C., Taliani, S., Settimo, F. D., Cosimelli, B., Greco, G., Novellino, E., & Martini, C. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.09.013 · Cited by 43
“For example, osteoporosis, characterized by low bone mass and structural deterioration of bone tissue with an increased susceptibility to fractures, is amajor public health threat to the elderly [2,3].”
Background
Preventing Bone Loss and Weight Gain with Combinations of Vitamin D and Phytochemicals
Lai, C., Yang, J., Rayalam, S., Della‐Fera, M. A., Ambati, S., Lewis, R. D., Hamrick, M. W., Hartzell, D. L., & Baile, C. A. (2011) · Journal of Medicinal Food · doi:10.1089/jmf.2010.0232 · Cited by 43
Osteoporosis and ageing affects the migration of stem cells and this is ameliorated by transfection with CXCR4
Sanghani‐Kerai, A., Coathup, M. J., Samazideh, S., et al. (2017) · Bone and Joint Research · doi:10.1302/2046-3758.66.bjr-2016-0259.r1 · Cited by 43
Icariin Regulates the Bidirectional Differentiation of Bone Marrow Mesenchymal Stem Cells through Canonical Wnt Signaling Pathway
Huang, J., Bao, Y., Xiang, W., Jing, X., Guo, J., Yao, X., Wang, R., & Guo, F. (2017) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2017/8085325 · Cited by 44
Nitric oxide mediates low magnesium inhibition of osteoblast-like cell proliferation
Leidi, M., Dellera, F., Mariotti, M., et al. (2011) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2011.06.016 · Cited by 43
“Osteoporosis results from complex interactions among local and systemic regulators of bone cell function [17].”
Background
Bone Sparing Effect of a Novel Phytoestrogen Diarylheptanoid from Curcuma comosa Roxb. in Ovariectomized Rats
Tantikanlayaporn, D., Wichit, P., Weerachayaphorn, J., Chairoungdua, A., Chuncharunee, A., Suksamrarn, A., & Piyachaturawat, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078739 · Cited by 43
“It is characterized by reduced bone mass and the deterioration of bone microarchitecture leading to increase the risk of bone fragility and fracture [3].”
Background
Evaluation of osteoclastic resorption activity using calcium phosphate coating combined with labeled polyanion
Miyazaki, T., Miyauchi, S., Anada, T., et al. (2010) · Analytical Biochemistry · doi:10.1016/j.ab.2010.11.014 · Cited by 42
Osteoporosis Associated With Pulmonary Silicosis in an Equine Bone Fragility Syndrome
Arens, A. M., Barr, B. C., Puchalski, S. M., Poppenga, R. H., Kulin, R. M., Anderson, J. D. C., & Stover, S. M. (2010) · Veterinary Pathology · doi:10.1177/0300985810385151 · Cited by 42
GDF11 Inhibits Bone Formation by Activating Smad2/3 in Bone Marrow Mesenchymal Stem Cells
Lu, Q., Tu, M., Li, C., Zhang, L., Jiang, T., Liu, T., & Luo, X. (2016) · Calcified Tissue International · doi:10.1007/s00223-016-0173-z · Cited by 43
“Osteoporosis is defined as a disease that weakens bone structure and increases the risk of fractures [7, 8].”
Background
Overlapping molecular pathways between cannabinoid receptors type 1 and 2 and estrogens/androgens on the periphery and their involvement in the pathogenesis of common diseases (Review)
Dobovišek, L., Hojnik, M., & Ferk, P. (2016) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2016.2779 · Cited by 42
“Imbalances in bone remodeling mechanisms cause one of the most common degenerative diseases in developed countries, osteoporosis (73).”
Background
When prostate cancer meets bone: Control by wnts
Emami, K. H., & Corey, E. (2007) · Cancer Letters · doi:10.1016/j.canlet.2006.12.040 · Cited by 42
Nothing but skin and bone
Ross, F. P. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28605 · Cited by 43
Cigarette smoke-associated inflammation impairs bone remodeling through NFκB activation
Lü, Y., Di, Y. P., Chang, M., Huang, X., Chen, Q., Hong, N., Kahkonen, B., Di, M. E., Yu, C., Keller, E. T., et al. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-02836-z · Cited by 44
“Inversely, the imbalance of bone formation and bone resorption leads to pathological bone loss, which subsequently results in bone-related diseases such as osteoporosis [16].”
Background
A review of minodronic acid hydrate for the treatment of osteoporosis
Tanishima, S., & Morio, Y. (2013) · Clinical Interventions in Aging · doi:10.2147/cia.s23927 · Cited by 41
“Introduction Osteoporosis is defined as a disease that weakens bone structure and increases the risk of fractures.(1,2) It is becoming a serious issue in our aging society because sufferers are likely to sustain fractures of the vertebrae or femoral neck.”
MiR-132 regulates osteogenic differentiation via downregulating Sirtuin1 in a peroxisome proliferator-activated receptor β/δ–dependent manner
Gong, K., Qu, B., Liao, D., Liu, D., Wang, C., Zhou, J., & Pan, X. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.07.057 · Cited by 41
Microtopography of Immune Cells in Osteoporosis and Bone Lesions by Endocrine Disruptors
Toni, R., Conza, G. D., Barbaro, F., Zini, N., Consolini, E., Dallatana, D., Antoniel, M., Quarantini, E., Quarantini, M., Maioli, S., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01737 · Cited by 40
Lasofoxifene, a new selective estrogen receptor modulator for the treatment of osteoporosis and vaginal atrophy
Gennari, L. (2009) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656560903127241 · Cited by 41
“In women, osteoporosis and fractures mainly occurs as a consequence of estrogen deficiency after menopause and results from an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts, leading to a net bone loss with each remodeling cycle [8-11].”
Background
Knee and hip radiographic osteoarthritis predict total hip bone loss in older adults: A prospective study
Ding, C., Cicuttini, F., Boon, C., et al. (2009) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.091012 · Cited by 41
“Hormonal factors such as estrogens((37,38)) and leptin((39,40)) play important roles in bone formation and cartilage hemostasis.”
Background
Impact of Osteoporosis and Its Treatment on Oral Health
Anil, S., Preethanath, R. S., AlMoharib, H. S., Kamath, K. P., & Anand, P. S. (2013) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e31828983da · Cited by 41
“Although bone remodeling is accelerated at menopause, this accelerated bone remodeling is associated with increased bone loss and impaired bone formation.(4) Estrogen deficiency may enhance the rate of bone loss by stimulating synthesis of several inflammatory cytokines that regulate osteoclast generation, such as int…”
Background
In vitro evaluation of the direct effect of estradiol on human osteoblasts (HOB) and human mesenchymal stem cells (h-MSCs)
Silvio, L. D., Jameson, J., Gamie, Z., Giannoudis, P. V., & Tsiridis, E. E. (2006) · Injury · doi:10.1016/j.injury.2006.08.022 · Cited by 41
Liquid–Liquid Phase Separation of Biomacromolecules and Its Roles in Metabolic Diseases
Chen, Z., Huai, Y., Mao, W., et al. (2022) · Cells · doi:10.3390/cells11193023 · Cited by 40
Oxytocin Reverses Osteoporosis in a Sex-Dependent Manner
Béranger, G. E., Djedaini, M., Battaglia, S., Roux, C. H., Scheideler, M., Heymann, D., Amri, E., & Pisani, D. F. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00081 · Cited by 39
Ajulemic acid, a nonpsychoactive cannabinoid acid, suppresses osteoclastogenesis in mononuclear precursor cells and induces apoptosis in mature osteoclast‐like cells
George, K. L., Saltman, L. H., Stein, G. S., Lian, J. B., & Zurier, R. B. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21263 · Cited by 40
Arginine Enhances Osteoblastogenesis and Inhibits Adipogenesis through the Regulation of Wnt and NFATc Signaling in Human Mesenchymal Stem Cells
Huh, J., Choi, J., Shin, Y.-O., Park, D., Kang, J., Nam, D., Choi, D., & Lee, J.-D. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150713010 · Cited by 40
“The current treatment of osteoporosis relies primarily on antiresorptive agents that inhibit osteoclastic bone resorption and anabolic agents that increase osteoblastic bone formation [2,28], but osteoporosis treatments have exhibited either limited success or adverse effects [29,30].”
Background
RETRACTED: Protective effects of casein-derived peptide VLPVPQK against hydrogen peroxide–induced dysfunction and cellular oxidative damage in rat osteoblastic cells
Mada, S., Reddi, S., Kumar, N. R., Kapila, S., & Kapila, R. (2017) · Human & Experimental Toxicology · doi:10.1177/0960327116678293 · Cited by 40
“Osteoporosis is the most prevalent systemic skeletal disorder, characterized by a low bone mineral density and microstructural deterioration of the bone tissue, leading to increase in bone fragility and risk of fracture.(2,3) Bone, a dynamic and metabolically active tissue which under physiological condition is contin…”
Background
Retracted
STAT-3 regulation of CXCR4 is necessary for the prenylflavonoid Icaritin to enhance mesenchymal stem cell proliferation, migration and osteogenic differentiation
Lim, R. Z. L., Li, L., Yong, E., & Chew, N. (2018) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2018.04.016 · Cited by 40
Role of P2×7 receptor in the differentiation of bone marrow stromal cells into osteoblasts and adipocytes
Li, W., Li, G., Zhang, Y., Wei, S., Song, M., Wang, W., Yuan, X., Wu, H. K., & Yang, Y. (2015) · Experimental Cell Research · doi:10.1016/j.yexcr.2015.10.011 · Cited by 41
Therapeutic Treatments for Osteoporosis—Which Combination of Pills Is the Best among the Bad?
Tonk, C. H., Shoushrah, S. H., Babczyk, P., Khaldi-Hansen, B. E., Schulze, M., Herten, M., & Tobiasch, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031393 · Cited by 44
Chinese patent medicine for osteoporosis: a systematic review and meta-analysis
Jia, Y., Sun, J., Zhao, Y., et al. (2022) · Bioengineered · doi:10.1080/21655979.2022.2038941 · Cited by 40
“In women, postmenopausal decline in estrogen levels is critical to the pathogenesis of OP, in addition to calcium and vitamin D deficiencies can also accelerate this process [52,53].”
Background
Nutritional Influences on Bone Health
Burckhardt, P., Dawson-Hughes, B. F., & Weaver, C. M. (2013) · Springer eBooks · doi:10.1007/978-1-4471-2769-7 · Cited by 40
Inhibitory effects of high glucose/insulin environment on osteoclast formation and resorption in vitro
Xu, F., Ye, Y., Dong, Y., Guo, F., Chen, A., & Huang, S. (2013) · Journal of Huazhong University of Science and Technology [Medical Sciences] · doi:10.1007/s11596-013-1105-z · Cited by 40
Creatine Supplementation (3 g/d) and Bone Health in Older Women: A 2-Year, Randomized, Placebo-Controlled Trial
Sales, L. P., Pinto, A. J., Rodrigues, S. F., Alvarenga, J. C., Gonçalves, N., Sampaio-Barros, M. M., Benatti, F. B., Gualano, B., & Rodrigues Pereira, R. M. (2020) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glz162 · Cited by 39
Advances in therapeutic applications of fish oil: A review
Das, P., Dutta, A., Panchali, T., Khatun, A., Kar, R., Das, T. K., Phoujdar, M., Chakrabarti, S., Ghosh, K., & Pradhan, S. (2024) · Measurement Food · doi:10.1016/j.meafoo.2024.100142 · Cited by 48
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The Positive Association between Peripheral Blood Cell Counts and Bone Mineral Density in Postmenopausal Women
Kim, H., Cho, H. Y., Park, I. Y., et al. (2011) · Yonsei Medical Journal · doi:10.3349/ymj.2011.52.5.739 · Cited by 39
Identification of Transcriptional Factors and Key Genes in Primary Osteoporosis by DNA Microarray
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“Normally, osteoclast cells resorb bone in bone marrow and deposit new bone by osteoblast [6].”
Injectable Hydrogels as Three-Dimensional Network Reservoirs for Osteoporosis Treatment
Zheng, Z., Yu, C., & Wei, H. (2020) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2020.0168 · Cited by 39
“Generally, an accelerated bone remodeling process results in a lower BMD of OP patients, 22 and further weak-ening of the bone takes place due to the presence of numerous unﬁlled Haversian canals and Howship’s lacunae 12 for the complete loss of trabecular structures as bone formation templates.”
The journey from white rice to ultra-high hydrostatic pressurized brown rice: an excellent endeavor for ideal nutrition from staple food
Hashimoto, M., Hossain, S., Matsuzaki, K., Shido, O., & Yoshino, K. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1844138 · Cited by 39
“with the ovarian estrogen hormone deficiency (Raisz 2005).”
Background
Converging functionality: Strategies for 3D hybrid-construct biofabrication and the role of composite biomaterials for skeletal regeneration
Alcala‐Orozco, C. R., Cui, X., Hooper, G. J., Lim, K. S., & Woodfield, T. B. F. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.03.008 · Cited by 40
Multiple pharmacological inhibitors targeting the epigenetic suppressor enhancer of zeste homolog 2 (Ezh2) accelerate osteoblast differentiation
Galvan, M. L., Paradise, C. R., Kubrova, E., Jerez, S., Khani, F., Thaler, R., Dudakovic, A., & van Wijnen, A. J. (2021) · Bone · doi:10.1016/j.bone.2021.115993 · Cited by 40
Fracture risk in the femoral hip region: A finite element analysis supported experimental approach
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“The affected patients’ bone mineral density (BMD) is drastically reduced, deteriorating the bones’ micostructural characteristics as a result of excessive bone resorption followed by insufficient bone formation during remodelling (Frost and Thomas, 1963; Raisz, 2005).”
Background
GPR120: A bi-potential mediator to modulate the osteogenic and adipogenic differentiation of BMMSCs
Gao, B., Huang, Q., Jie, Q., Lu, W., Wang, L., Li, X., Sun, Z., Hu, Y., Chen, L., Liu, B., et al. (2015) · Scientific Reports · doi:10.1038/srep14080 · Cited by 39
Impaired osteoblast and osteoclast function characterize the osteoporosis of Snyder - Robinson syndrome
Albert, J. S., Bhattacharyya, N., Wolfe, L. A., Bone, W. P., Maduro, V. V. B., Accardi, J., Adams, D. R., Schwartz, C. E., Norris, J. W., Wood, T. C., et al. (2015) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-015-0235-8 · Cited by 38
“Osteoporosis arises from disruption of the equilibrium between osteoclastic bone resorption and osteoblastic bone formation [18], which is regulated by mechanical and endocrine stimuli [19].”
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RANKL Is a Mediator of Bone Resorption in Idiopathic Hypercalciuria
Gomes, S. A., dos Reis, L. M., Noronha, I. D. L., Jorgetti, V., & Heilberg, I. P. (2008) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.00240108 · Cited by 39
“TGF- is known as the most important and abundant growth factor in bone matrix, stimulating bone formation, mineralization, and inhibiting bone resorption through a proapoptotic effect on mature osteoclasts and inhibition of osteoclast differentiation (27,28); however, an experimental study in calvarie culture suggeste…”
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Different expression patterns of organic anion transporting polypeptides in osteosarcomas, bone metastases and aneurysmal bone cysts
Thalhammer (2009) · Oncology Reports · doi:10.3892/or_00000591 · Cited by 38
A New Inflammatory Marker for Bone Loss and Low Bone Mineral Density: Platelet-Tolymphocyte Ratio
Köseoğlu, S. B. (2016) · Biomarkers in Medicine · doi:10.2217/bmm-2016-0188 · Cited by 38
Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss
Granchi, D., Torreggiani, E., Massa, A., Caudarella, R., Pompo, G. D., & Baldini, N. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181230 · Cited by 37
Adipose mesenchymal stem cells from osteoporotic donors preserve functionality and modulate systemic inflammatory microenvironment in osteoporotic cytotherapy
Zheng, C., Sui, B., Liu, N., Hu, C., He, T., Zhang, X., Zhao, P., Chen, J., Xuan, K., & Jin, Y. J. (2018) · Scientific Reports · doi:10.1038/s41598-018-23098-8 · Cited by 38
The Potential Role of miRNAs as New Biomarkers for Osteoporosis
Materozzi, M., Merlotti, D., Gennari, L., & Bianciardi, S. (2018) · International Journal of Endocrinology · doi:10.1155/2018/2342860 · Cited by 41
“Aging, as well as the presence of predisposing conditions, may cause either an unbalance in bone remodeling with an increased bone resorption not equally compensated by bone formation, or an increased remodeling velocity, leading to low bone mass, reduced strength, and deterioration of the skeletal microarchitecture […”
Background
miR-16-2* Interferes with WNT5A to Regulate Osteogenesis of Mesenchymal Stem Cells
Duan, L., Zhao, H., Xiong, Y., Tang, X., Yang, Y., Hu, Z., Li, C., Chen, S., & Yu, X. X. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000495489 · Cited by 38
Long non‑coding RNA MEG3 is involved in osteogenic differentiation and bone diseases (Review)
Sun, H., Peng, G., Wu, H., Liu, M., Mao, G., Ning, X., Yang, H., & Deng, J. (2020) · Biomedical Reports · doi:10.3892/br.2020.1305 · Cited by 37
“The major mechanism underlying PMOP involves an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts (61).”
Background
Moderate SMFs attenuate bone loss in mice by promoting directional osteogenic differentiation of BMSCs
Chen, G., Zhuo, Y., Tao, B., Liu, Q., Shang, W., Li, Y., Wang, Y., Li, Y., Zhang, L., Fang, Y., et al. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-02004-y · Cited by 38
Cell Sources for Human In vitro Bone Models
Ansari, S., Ito, K., & Hofmann, S. (2021) · Current Osteoporosis Reports · doi:10.1007/s11914-020-00648-6 · Cited by 37
Association between prolonged breastfeeding and bone mineral density and osteoporosis in postmenopausal women: KNHANES 2010-2011
Hwang, I.-R., Choi, Y., Lee, W. K., et al. (2015) · Osteoporosis International · doi:10.1007/s00198-015-3292-x · Cited by 37
“Osteoporosis is a metabolic bone disease associated with the micro-architectural deterioration of bone mass [1].”
Background
Polymorphism of LRP 5 gene and emphysema severity are associated with osteoporosis in J apanese patients with or at risk for COPD
Chubachi, S., Nakamura, H., Sasaki, M., et al. (2014) · Respirology · doi:10.1111/resp.12429 · Cited by 37
Influence of Extracellular Vesicles Isolated From Osteoblasts of Patients With Cox-Arthrosis and/or Osteoporosis on Metabolism and Osteogenic Differentiation of BMSCs
Niedermair, T., Lukas, C., Li, S., Stöckl, S., Craiovan, B. S., Brochhausen, C., Federlin, M., Herrmann, M., & Grässel, S. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.615520 · Cited by 38
“Changes in estrogen signaling play a major role in progression of postmenopausal osteoporosis (Raisz, 2005; Weitzmann and Pacifici, 2006).”
Background
Correlation between Absence of Bone Remodeling Compartment Canopies, Reversal Phase Arrest, and Deficient Bone Formation in Post-Menopausal Osteoporosis
Andersen, T. L., Hauge, E., Rolighed, L., Bollerslev, J., Kjærsgaard‐Andersen, P., & Delaissé, J. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.12.005 · Cited by 39
“PMO is, on the other hand, both a systemic and a heterogeneous bone disease induced by multiple factors related to aging and the postmenopausal condition.(33) Therefore, one might hypothesize that the destabilization of the osteoblastic BRC canopies in PMO results from the post-menopausal estrogen deficiency, which is…”
Background
Panax Notoginseng Saponins Promote Osteogenic Differentiation of Bone Marrow Stromal Cells Through the ERK and P38 MAPK Signaling Pathways
Li, X., Liu, Z.-Y., Chang, B., et al. (2011) · Cellular Physiology and Biochemistry · doi:10.1159/000331753 · Cited by 37
Pueraria lobate Inhibits RANKL-Mediated Osteoclastogenesis Via Downregulation of CREB/PGC1β/c-Fos/NFATc1 Signaling
Park, K. H., Gu, D. R., Jin, S. H., Yoon, C., Ko, W., Kim, Y. C., & Lee, S. H. (2017) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x17500938 · Cited by 37
Low skeletal muscle mass associates with low femoral neck strength, especially in older Korean women: the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV)
Kim, B., Ahn, S. H., Kim, H. M., Lee, S. H., & Koh, J. (2014) · Osteoporosis International · doi:10.1007/s00198-014-2959-z · Cited by 37
“There is substantial evidence for the notion that estrogen deficiency during menopause can cause relative increases in osteoclastic bone resorption, both directly (by affecting the bone cells) and indirectly (via diverse mechanisms such as ROS, cytokines, and growth factors) [44].”
Background
Ursodeoxycholic acid decreases bilirubin‐induced osteoblast apoptosis
Ruiz-Gaspà, S., Dubreuil, M., Guañabens, N., Combalía, A., Peris, P., Monegal, A., & Parés, A. R. (2014) · European Journal of Clinical Investigation · doi:10.1111/eci.12355 · Cited by 34
Weak Epistasis Generally Stabilizes Phenotypes in a Mouse Intercross
Tyler, A. L., Donahue, L. R., Churchill, G. A., & Carter, G. W. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005805 · Cited by 34
Transplantation of osteoporotic bone marrow stromal cells rejuvenated by the overexpression of SATB2 prevents alveolar bone loss in ovariectomized rats
Xu, R., Fu, Z., Liu, X., Xiao, T., Zhang, P., Du, Y., Yuan, H., Cheng, J., & Jiang, H. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.09.001 · Cited by 35
Total flavonoids of Rhizoma Drynariae combined with calcium attenuate osteoporosis by reducing reactive oxygen species generation
Mu, P., Hu, Y., Ma, X., et al. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10050 · Cited by 36
“Osteoporosis(OP) is a systemic bone metabolic disorder, which is characterized by decreased bone density and degeneration of the bone microstructure, resulting in increased bone brittleness and risk of fractures (1).”
Background
Advanced oxidation protein products accelerate bone deterioration in aged rats
Zeng, J., Zhong, Z., Li, X., et al. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.11.014 · Cited by 36
Hepatic Osteodystrophy Is Common in Patients with Noncholestatic Liver Disease
Choudhary, N. S., Tomar, M., Chawla, Y. K., Bhadada, S. K., Khandelwal, N. K., Dhiman, R. K., Duseja, A. K., & Bhansali, A. K. (2011) · Digestive Diseases and Sciences · doi:10.1007/s10620-011-1722-y · Cited by 36
“Vitamin D deficiency and secondary hyperparathyroidism can contribute to accelerated bone loss, increasing fragility, and neuromuscular impairment that can increase the risk of falls [8].”
Background
Claudin 18 is a novel negative regulator of bone resorption and osteoclast differentiation
Linares, G. R., Brommage, R., Powell, D. R., Xing, W., Chen, S., Alshbool, F. Z., Lau, K. ‐. W., Wergedal, J. E., & Mohan, S. (2012) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.1600 · Cited by 37
Anthocyanin-Rich Blackcurrant Extract Attenuates Ovariectomy-Induced Bone Loss in Mice
Zheng, X., Mun, S. H., Lee, S. G., Vance, T. M., Hubert, P. A., Koo, S. I., Lee, S., & Chun, O. K. (2016) · Journal of Medicinal Food · doi:10.1089/jmf.2015.0148 · Cited by 37
“21,22 In this study, we attempted to examine whether blackcurrant anthocyanins can alleviate ovariectomy-induced bone loss.”
Induction of Senile Osteoporosis in Normal Mice by Intra-Bone Marrow-Bone Marrow Transplantation from Osteoporosis-Prone Mice
Ueda, Y., Inaba, M., Takada, K., Fukui, J., Sakaguchi, Y., Tsuda, M., Omae, M., Kushida, T., Iida, H., & Ikehara, S. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0811 · Cited by 36
Conditional Disruption of the Prolyl Hydroxylase Domain-Containing Protein 2 (Phd2) Gene Defines Its Key Role in Skeletal Development
Cheng, S., Xing, W., Pourteymoor, S., & Mohan, S. (2014) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2258 · Cited by 35
“Two major factors cause osteoporosis: low peak BMD, which is achieved at the end of adolescence, and a high bone loss rate, which typically occurs after menopause and during aging.((1,2)) Identifying genes that influence peak BMD and bone accretion is crucial for understanding the molecular mechanisms of bone formatio…”
Background
Potential role of odanacatib in the treatment of osteoporosis
Ng, K. W. (2012) · Clinical Interventions in Aging · doi:10.2147/cia.s26729 · Cited by 35
The use of delta-tocotrienol and lovastatin for anti-osteoporotic therapy
Abdul-Majeed, S., Mohamed, N., & Soelaiman, I. N. (2014) · Life Sciences · doi:10.1016/j.lfs.2014.12.012 · Cited by 35
Therapeutical Potential of CB2 Receptors in Immune-Related Diseases
Leleu‐Chavain, N., Desreumaux, P., Chavatte, P., & Millet, R. (2014) · Current Molecular Pharmacology · doi:10.2174/1874467207666140219122337 · Cited by 37
“Osteoporosis is a metabolic disorder characterized by poor bone mass and bone degradation, including fractures, morbidity and mortality [235].”
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Lack of Schnurri-2 Expression Associates with Reduced Bone Remodeling and Osteopenia
Saita, Y., Takagi, T., Kitahara, K., Usui, M., Miyazono, K., Ezura, Y., Nakashima, K., Kurosawa, H., Ishii, S., & Noda, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611203200 · Cited by 35
Transcriptomic characterization of signaling pathways associated with osteoblastic differentiation of MC-3T3E1 cells
Luttrell, L. M., Dar, M. S., Gesty‐Palmer, D., El‐Shewy, H. M., Robinson, K. M., Haycraft, C. J., & Barth, J. L. (2019) · PLoS ONE · doi:10.1371/journal.pone.0204197 · Cited by 34
Proanthocyanidin-rich grape seed extract improves bone loss, bone healing, and implant osseointegration in ovariectomized animals
Tenkumo, T., Aobulikasimu, A., Asou, Y., Shirato, M., Shishido, S., Kanno, T., Niwano, Y., Sasaki, K., & Nakamura, K. (2020) · Scientific Reports · doi:10.1038/s41598-020-65403-4 · Cited by 35
Identification of the canonical and noncanonical role of miR-143/145 in estrogen-deficient bone loss
Xu, R., Shen, X., Xie, H., Zhang, H., Liu, D., Chen, X., Fu, Y., Zhang, P., Yang, Y. A., Cheng, J., et al. (2021) · Theranostics · doi:10.7150/thno.55041 · Cited by 36
“Most drugs for the treatment of postmenopausal osteoporosis suppress bone resorption, which can lead to many long-term side effects such as osteonecrosis [42, 43].”
Background
Photon-counting detector CT and energy-integrating detector CT for trabecular bone microstructure analysis of cubic specimens from human radius
Klintström, B., Henriksson, L., Moreno, R., et al. (2022) · European Radiology Experimental · doi:10.1186/s41747-022-00286-w · Cited by 35
“Background Osteoporosis is a skeletal disease where multiple pathogenic processes lead to loss of bone mass and changes in the microarchitecture [1].”
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Molecular Aspects of Bone Remodeling
Alma, Y., Valdés‐Flores, M., Orozco, L., & Velzquez-Cruz, R. (2013) · InTech eBooks · doi:10.5772/54905 · Cited by 42
“Recent studies indicate that significant trabecular bone loss begins as early as the twenties in men and women long before any major hormonal changes [95].”
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A novel carborane analog, BE360, with a carbon-containing polyhedral boron-cluster is a new selective estrogen receptor modulator for bone
Hirata, M., Inada, M., Matsumoto, C., Takita, M., Ogawa, T., Endo, Y., & Miyaura, C. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.01.033 · Cited by 36
Effects of Denosumab on Bone Mineral Density and Bone Turnover in Postmenopausal Women
Wensel, T. M., Iranikhah, M., & Wilborn, T. W. (2011) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.31.5.510 · Cited by 36
“increase the rate of bone remodeling result in net bone loss over time.(12) In adults, approximately”
Background
Ovariectomy worsens secondary hyperparathyroidism in mature rats during low-Ca diet
Zhang, Y., Lai, W., Wu, C., et al. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00445.2006 · Cited by 35
“During menopause, the increased Ca requirements due to poor intestinal absorption and increased urinary loss are complicated by the age-related abnormalities of the vitamin Dendocrine system, including secondary hyperparathyroidism, intestinal resistance to 1,25(OH)2D3, and decreased 1,25(OH)2D3 production due to impa…”
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Evaluating resveratrol as a therapeutic bone agent: preclinical evidence from rat models of osteoporosis
Tou, J. C. L. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12840 · Cited by 34
Effects and Interaction of Icariin, Curculigoside, and Berberine in Er-Xian Decoction, a Traditional Chinese Medicinal Formula, on Osteoclastic Bone Resorption
Xue, L., Jiao, L., Wang, Y., Nie, Y. G., Han, T., Jiang, Y., Rahman, K., Zhang, Q., & Qin, L. (2012) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2012/490843 · Cited by 33
Preventive effects of withaferin A isolated from the leaves of an Indian medicinal plant Withania somnifera (L.): Comparisons with 17-β-estradiol and alendronate
Khedgikar, V., Ahmad, N., Kushwaha, P., Gautam, J., Nagar, G. K., Singh, D. R., Trivedi, P. K., Mishra, P. R., Sangwan, N. S., & Trivedi, R. (2014) · Nutrition · doi:10.1016/j.nut.2014.05.010 · Cited by 34
“Postmenopausal osteoporosis is characterized by reduced bone mass and microarchitectural deterioration [8] because of estrogen cessation.”
Background
Suppression of zinc finger protein 467 alleviates osteoporosis through promoting differentiation of adipose derived stem cells to osteoblasts
Li, Y., Pan, L., Chen, L., Chen, J., Zhang, X., Lv, Z., & Fu, D. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-11 · Cited by 34
“Osteoporosis is a prevalent bone disease that is characterized by loss of bone mass and strength, leading to fragility fracture [23].”
17β-Estradiol inhibits ER stress-induced apoptosis through promotion of TFII-I-dependent Grp78 induction in osteoblasts
Guo, Y., Sun, Z., Ma, J., et al. (2014) · Laboratory Investigation · doi:10.1038/labinvest.2014.63 · Cited by 34
Muscle-derived factors influencing bone metabolism
Gries, K. J., Zysik, V. S., Jobe, T. K., Griffin, N., Leeds, B. P., & Lowery, J. W. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.10.009 · Cited by 39
The role of melatonin in bone regeneration: A review of involved signaling pathways
Malakoti, F., Zare, F., Zarezadeh, R., Sadigh, A. R., Sadeghpour, A., Majidinia, M., Yousefi, B., & Alemi, F. (2022) · Biochimie · doi:10.1016/j.biochi.2022.08.008 · Cited by 36
Chapter 6 Vascular Calcification Inhibitors In Relation To Cardiovascular Disease With Special Emphasis On Fetuin‐A In Chronic Kidney Disease
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Concerted stimuli regulating osteo-chondral differentiation from stem cells: phenotype acquisition regulated by microRNAs
Gordeladze, J. O., Djouad, F., Brondello, J., Noël, D., Duroux-Richard, I., Apparailly, F., & Jørgensen, C. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2009.143 · Cited by 36
Glycyrrhizic acid (GCA) as 11β-hydroxysteroid dehydrogenase inhibitor exerts protective effect against glucocorticoid-induced osteoporosis
Ramli, E. S. M., Suhaimi, F., Asri, S. F. M., Ahmad, F., & Soelaiman, I. (2013) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-012-0413-x · Cited by 33
“Changes are more pronounced at the appendicular skeleton compared to the spine and bone loss in glucocorticoid induced osteoporosis is most pronounced in trabecular bone and in the cortical shell of the vertebral body [1].”
BackgroundInfluential
Osteoporosis Risk in Patients With Chronic Obstructive Pulmonary Disease: The EOLO Study
Maggi, S., Siviero, P., Gonnelli, S., Schiraldi, C., Malavolta, N., Nuti, R., & Crepaldi, G. (2009) · Journal of Clinical Densitometry · doi:10.1016/j.jocd.2009.05.003 · Cited by 33
Prolidase activity and oxidative status in patients with thalassemia major
Çakmak, A., Söker, M., Ahmet, K., et al. (2010) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.20361 · Cited by 34
Extract of Magnoliae Flos inhibits ovariectomy-induced osteoporosis by blocking osteoclastogenesis and reducing osteoclast-mediated bone resorption
Jun, A. Y., Kim, H., Park, K.-K., et al. (2012) · Fitoterapia · doi:10.1016/j.fitote.2012.08.020 · Cited by 34
“Osteoporosis is characterized by a reduced mass density and deteriorated trabecular bone microarchitecture, with a resulting increase in fracture risk [17].”
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Effects of Remifemin Treatment on Bone Integrity and Remodeling in Rats with Ovariectomy-Induced Osteoporosis
Cui, G., Leng, H., Wang, K., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082815 · Cited by 34
“This may be due to loss of the bone formation template, which is massively damaged as bone reabsorption increases following ovariectomy [45].”
Background

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

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