Cortical-Bone Fragility — Insights from sFRP4 Deficiency in Pyle’s Disease
Open accessAbstract
BACKGROUND: Cortical-bone fragility is a common feature in osteoporosis that is linked to nonvertebral fractures. Regulation of cortical-bone homeostasis has proved elusive. The study of genetic disorders of the skeleton can yield insights that fuel experimental therapeutic approaches to the treatment of rare disorders and common skeletal ailments. METHODS: We evaluated four patients with Pyle's disease, a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and fractures; two patients were examined by means of exome sequencing, and two were examined by means of Sanger sequencing. After a candidate gene was identified, we generated a knockout mouse model that manifested the phenotype and studied the mechanisms responsible for altered bone architecture. RESULTS: In all affected patients, we found biallelic truncating mutations in SFRP4, the gene encoding secreted frizzled-related protein 4, a soluble Wnt inhibitor. Mice deficient in Sfrp4, like persons with Pyle's disease, have increased amounts of trabecular bone and unusually thin cortical bone, as a result of differential regulation of Wnt and bone morphogenetic protein (BMP) signaling in these two bone compartments. Treatment of Sfrp4-deficient mice with a soluble Bmp2 receptor (RAP-661) or with antibodies to sclerostin corrected the cortical-bone defect. CONCLUSIONS: Our study showed that Pyle's disease was caused by a deficiency of sFRP4, that cortical-bone and trabecular-bone homeostasis were governed by different mechanisms, and that sFRP4-mediated cross-regulation between Wnt and BMP signaling was critical for achieving proper cortical-bone thickness and stability. (Funded by the Swiss National Foundation and the National Institutes of Health.).
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sFRP4 is known to be a Wnt regulator, and mutations in SFRP4 in humans have been shown to cause Pyle disease, which is characterized by cortical bone fragility and fractures.
“sFRP4 is known to be a Wnt regulator, and mutations in SFRP4 in humans have been shown to cause Pyle disease, which is characterized by cortical bone fragility and fractures (45).”
From Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight (2020) · cites this paper as [45]
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Movérare‐Skrtic, S., Nilsson, K. H., Henning, P., Funck‐Brentano, T., Nethander, M., Rivadeneira, F., Nunes, G. C., Koskela, A., Tuukkanen, J., Tuckermann, J. P., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900707r · Cited by 32 · see citing works
“Although progress has been made in therapeutic approaches to reduce the risk of vertebral fracture (which occurs at sites rich in trabecular bone), currently available treatments do little to reduce the risk of nonvertebral fracture, which results mostly from cortical bone fragility (4, 43, 45, 46).”
Kamizaki, K., Endo, M., Minami, Y., & Kobayashi, Y. (2020) · Developmental Dynamics · doi:10.1002/dvdy.151 · Cited by 32 · see citing works
“A possible mechanism by which Sfrp4 regulates cortical thickness is proposed as follows: Wnt5a increases the expression of BMP2, which in turn promotes the expression of canonical Wnt inhibitor sclerostin.(92) Increased sclerostin expression suppresses bone accrual in cortical bone.”
BackgroundThe role of wnt signaling in diabetes-induced osteoporosis
Bao, K., Jiao, Y., Xing, L., Zhang, F., & Tian, F. (2023) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-023-01067-0 · Cited by 31 · see citing works
“The loss of canonical Wnt signaling pathway inhibition in SFRP4-KO mice caused increases in bone trabecular bone mass [92].”
BackgroundHe, G., Shi, Y., Lim, J., Bellido, T., Ni, J., & Long, F. (2017) · Bone Research · doi:10.1038/boneres.2017.16 · Cited by 31 · see citing works
A novel sequence variant in SFRP4 causing Pyle disease
Galada, C., Shah, H. H., Shukla, A., & Girisha, K. M. (2017) · Journal of Human Genetics · doi:10.1038/jhg.2016.166 · Cited by 29 · see citing works
Self-citationSFRP4 gene expression is increased in aggressive prostate cancer
Sandsmark, E., Andersen, M., Bofin, A. M., Bertilsson, H., Drabløs, F., Bathen, T. F., Rye, M. B., & Tessem, M. (2017) · Scientific Reports · doi:10.1038/s41598-017-14622-3 · Cited by 29 · see citing works
Azuma, K., Zhou, Q., & Kubo, K. (2018) · Medical Molecular Morphology · doi:10.1007/s00795-018-0188-9 · Cited by 28 · see citing works
“Treatment with a Bmp2 receptor or antibody to sclerostin correlated the cortical bone defect [56].”
BackgroundInfluentialMechanistic insights into skeletal development gained from genetic disorders
Yip, R. K. H., Chan, D. T.-M., & Cheah, K. S. E. (2019) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2019.02.002 · Cited by 26 · see citing works
Guo, L. Z., Iida, A., Bhavani, G. S., Gowrishankar, K., Wang, Z., Xue, J.-Y., Wang, J., Miyake, N., Matsumoto, N., Hasegawa, T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22340-8 · Cited by 27 · see citing works
“The study was approved by the ethical committee of RIKEN, Kasturba Hospital, Manipal, and participating institutions (approval number: 17-16-40(3)).”
MethodSelf-citationBone Formation and the Wnt Signaling Pathway
Gori, F., Superti‐Furga, A., & Baron, R. (2016) · New England Journal of Medicine · doi:10.1056/nejmc1609768 · Cited by 27 · see citing works
Self-citationBoudin, E., & Hul, W. V. (2018) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2018.06.003 · Cited by 26 · see citing works
Mice lacking plastin-3 display a specific defect of cortical bone acquisition
Yorgan, T. A., Sari, H., Rolvien, T., Windhorst, S., Failla, A. V., Kornak, U., Oheim, R., Amling, M., & Schinke, T. (2019) · Bone · doi:10.1016/j.bone.2019.115062 · Cited by 26 · see citing works
A primer on skeletal dysplasias
Handa, A., Nishimura, G., Zhan, M. X., Bennett, D. L., & El-Khoury, G. Y. (2021) · Japanese Journal of Radiology · doi:10.1007/s11604-021-01206-5 · Cited by 25 · see citing works
“Metaphyseal dysplasia (Pyle disease) is characterized by striking metaphyseal broadening of the tubular bones [35, 36].”
BackgroundSelf-citationTsourdi, E. A., Lademann, F., Ominsky, M. S., Rijntjes, E., Köhrle, J., Misof, B. M., Roschger, P., Klaushofer, K., Hofbauer, L. C., & Rauner, M. (2017) · Endocrinology · doi:10.1210/en.2017-00247 · Cited by 25 · see citing works
WNT16 overexpression partly protects against glucocorticoid-induced bone loss
Ohlsson, C., Nilsson, K. H., Henning, P., Wu, J., Gustafsson, K. L., POUTANEN, M. H., Lerner, U. H., & Movérare‐Skrtic, S. (2018) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00292.2017 · Cited by 25 · see citing works
Brommage, R., Powell, D. R., & Vogel, P. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.038224 · Cited by 21 · see citing works
Self-citationTranslational studies provide insights for the etiology and treatment of cortical bone osteoporosis.
Brommage, R., & Ohlsson, C. (2018) · Best practice & research. Clinical endocrinology & metabolism · doi:10.1016/j.beem.2018.02.006 · Cited by 22 · see citing works
Self-citationNagano, K., Yamana, K., Saito, H., Kiviranta, R., Pedroni, A. C. F., Raval, D., Niehrs, C., Gori, F., & Baron, R. (2022) · eLife · doi:10.7554/elife.84171 · Cited by 20 · see citing works
Self-citationA novel homozygous truncating mutation of the SFRP4 gene in Pyle's disease
Chatron, N., Lesca, G., Labalme, A., Rollat‐Farnier, P., Monin, P., Pichot, E., Edery, P., Sanlaville, D., & Rossi, M. (2017) · Clinical Genetics · doi:10.1111/cge.12907 · Cited by 19 · see citing works
“The three mutations previously described in two Turkish siblings and two unrelated patients, respectively, of Japanese and Indian origin (3), were all truncating and affecting the SFRP4 netrin-like domain.”
BackgroundInfluentialKaya, S., Schurman, C. A., Dole, N. S., Evans, D. S., & Alliston, T. N. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4516 · Cited by 20 · see citing works
“In addition, Sfrp4, Meox1, and Epdr1 have been shown in several functional studies to play important roles in osteoclasts or osteoblasts((68-70)) and to participate in human diseases: Sfrp4 deficiency causes Pyle’s syndrome((71)) and Meox1-deficient zebrafish resemble human Klippel-Feil Syndrome.”
BackgroundUttarilli, A., Shah, H. H., Bhavani, G. S., Upadhyai, P., Shukla, A., & Girisha, K. M. (2018) · Bone · doi:10.1016/j.bone.2018.10.026 · Cited by 19 · see citing works
Self-citationSfrp4 and the Biology of Cortical Bone
Chen, R., Baron, R., & Gori, F. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00727-w · Cited by 19 · see citing works
Self-citationSfrp4 is required to maintain Ctsk-lineage periosteal stem cell niche function
Chen, R., Dong, H., Raval, D., Maridas, D. E., Baroi, S., Chen, K., Hu, D. Z., Berry, S. R., Baron, R., Greenblatt, M. B., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2312677120 · Cited by 17 · see citing works
“Cortical expansion, thickness, and porosity are critical determinants of bone strength in several species including humans (8, 16, 24, 43–48).”
InfluentialSelf-citationImproving Bone Health by Optimizing the Anabolic Action of Wnt Inhibitor Multitargeting
Choi, R. B., Bullock, W. A., Hoggatt, A. M., Loots, G. G., Genetos, D. C., & Robling, A. G. (2021) · JBMR Plus · doi:10.1002/jbm4.10462 · Cited by 16 · see citing works
“For example, whereas sclerostin((1)) affects all bone compartments, sFrp4((16)) has opposing effects on cortical versus cancellous bone, andWise((9)) andWnt16((17)) selectively alter cortical bone inmice.”
BackgroundHigh Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench
Bergen, D. J. M., Maurizi, A., Formosa, M. M., McDonald, G. L. K., El‐Gazzar, A., Hassan, N., Brandi, M. L., Riancho, J. A., Rivadeneira, F., Ntzani, E., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4715 · Cited by 16 · see citing works
“in Pyle’s disease (OMIM 265900), which is characterized by cortical thinning but increased trabecular bone mass.((26)) These variants in SFRP4 led to enhanced signaling in both the canonical and noncanonical arms of the pathway.”
BackgroundKındış, E., Şimşek‐Kiper, P. Ö., Koşukçu, C., Taşkıran, E. Z., Göçmen, R., Ütine, E., Haliloğlu, G., Boduroğlu, K., & Alikaşifoğlu, M. (2021) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62179 · Cited by 16 · see citing works
Roles of osteoclasts in pathological conditions
Kitazawa, S., Haraguchi, R., & Kitazawa, R. (2024) · Pathology International · doi:10.1111/pin.13500 · Cited by 15 · see citing works
“69 In human cases of Pyle's disease, the phenotype resembles that of sFRP4 knockout mice, which exhibit thicker bones that are nonetheless fragile and susceptible to fractures.”
Marie, P. J., & Cohen-Solal, M. E. (2017) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3356 · Cited by 15 · see citing works
“It was recently found that trabecular and cortical bone structures are controlled by distinct Wnt molecules,((123,124)) opening the area of novel targeted therapies for specific bone structures.”
BackgroundChoi, R. B., Bullock, W. A., Hoggatt, A. M., Horan, D. J., Pemberton, E. Z., Hong, J. M., Zhang, X., He, X., & Robling, A. G. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4411 · Cited by 13 · see citing works
“This is a curious but not unexpected finding, as other genes in the Wnt pathway exhibit compartment-specific effects on the skeleton.((15-17)) The cellular/molecular mechanisms driving Notum’s compartment selectivity are not known, but conceptually they could be harnessed in a therapeutic context to selectively manipu…”
BackgroundSclerostin antibody inhibits skeletal deterioration in mice exposed to partial weight-bearing
Spatz, J., Ellman, R., Cloutier, A., Louis, L. D., van Vliet, M., Dwyer, D., Stolina, M., Ke, H. Z., & Bouxsein, M. (2017) · Life Sciences in Space Research · doi:10.1016/j.lssr.2017.01.001 · Cited by 14 · see citing works
Inhibition of miR‑194 suppresses the Wnt/β‑catenin signalling pathway in gastric cancer
Peng, Y., Zhang, X., Lin, H., Deng, S., Huang, Y., Qin, Y., Feng, X., Yan, R., Zhao, Y., Cheng, Y., et al. (2018) · Oncology Reports · doi:10.3892/or.2018.6773 · Cited by 13 · see citing works
“Wnt-associated genes SFRP (29,30), nemo-like kinase (31), pygopus family PHD finger 2 (32,33), FBXW11 (34), PITX2 (35,36), FRAT genes (37) and transducer-like enhancer of split genes (38); signal transducers Dickkopf Wnt signalling pathway inhibitors (39), chibby family member 1, β -catenin antagonist (40) and kringle…”
InfluentialMoor, M. B., Ramakrishnan, S. K., Legrand, F., Dolder, S., Siegrist, M., Durussel, F., Centeno, G., Firsov, D., Hynes, N. E., Hofstetter, W., et al. (2018) · JBMR Plus · doi:10.1002/jbm4.10034 · Cited by 12 · see citing works
“Alternatively, disorders of the Wnt pathway have shown diverging phenotypes of cortical versus trabecular bone.((38)) In summary, a combination of both impaired growth factor signaling affecting the growth plate region and ALP dysfunction may contribute to the opposite cortical and trabecular”
BackgroundGenetics of Skeletal Disorders
Hannan, F. M., Newey, P. J., Whyte, M. P., & Thakker, R. V. (2020) · Handbook of experimental pharmacology · doi:10.1007/164_2020_350 · Cited by 12 · see citing works
Blouin, S., Fratzl‐Zelman, N., Roschger, A., Cabral, W. A., Klaushofer, K., Marini, J. C., Fratzl, P., & Roschger, P. (2018) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2018.10.010 · Cited by 12 · see citing works
“[PubMed: 15388305] Simsek Kiper PO, Saito H, Gori F, Unger S, Hesse E, Yamana K, Kiviranta R, Solban N, Liu J, Brommage R, Boduroglu K, Bonafe L, Campos-Xavier B, Dikoglu E, Eastell R, Gossiel F, Harshman K, Nishimura G, Girisha KM, Stevenson BJ, Takita H, Rivolta C, Superti-Furga A, Baron R, 2016 Cortical-bone fragil…”
BackgroundThe Crucial Role of the WNT System in Bone Remodelling
Grigorie, D. (2018) · Acta Endocrinologica (Bucharest) · doi:10.4183/aeb.2018.90 · Cited by 11 · see citing works
“Recently it has been shown that this disease is caused by recessive mutations in the SFRP4 gene (23).”
BackgroundMashhadikhan, M., Kheiri, H., & Dehghanifard, A. (2020) · Journal of Oral Biosciences · doi:10.1016/j.job.2020.08.001 · Cited by 11 · see citing works
Jansen, S., Baulain, U., Habig, C., Ramzan, F., Schauer, J., Schmitt, A. O., Scholz, A. M., Sharifi, A. R., Weigend, A., & Weigend, S. (2021) · Genes · doi:10.3390/genes12050702 · Cited by 11 · see citing works
“The estimates ranged from −0.02 to 0.017 g/cm2 for the BMD-related SNPs and from −16.70 to 15.70 N for the markers associated with the BBS. Effects of complete dominance were observed for the SNPs AX-76044166 (MPP7), AX-75711229 (ASPN), AX-75597497 (SMAD6) and AX-76099065 (SFRP4), with one copy of the major allele mas…”
BackgroundInfluentialSun, S., Liu, Y., Sun, J., Zan, B., Cui, Y., Jin, A., Xu, H., Huang, X., Zhu, Y., Yang, Y., et al. (2024) · Bone Research · doi:10.1038/s41413-024-00353-5 · Cited by 10 · see citing works
“Among the screened genes, we noticed Sfrp4 , the human pathogenic gene for osteopetrosis, 31 was downregulated in Osx Cre ;R26 dn/dn osteoblasts.”
BackgroundSelf-citationThe Intricacies of Renal Phosphate Reabsorption—An Overview
Walker, V. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094684 · Cited by 8 · see citing works
“Ultimately, these must be married to the renal findings to obtain a more complete picture to optimise therapy.”
BackgroundSowińska‐Seidler, A., Sztromwasser, P., Zawadzka, K., Sielski, D., Bukowska‐Olech, E., Zawadzki, P., Kozlowski, K. S., & Jamsheer, A. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.593407 · Cited by 10 · see citing works
“The authors showed that sFRP-4 differentially downregulates the canonical and non-canonical Wnt signaling in both compartments of the bone, allowing for the proper bone thickness and strength (Haraguchi et al., 2016; Kiper et al., 2016; Chen et al., 2019).”
BackgroundKhouri‐Farah, N., Winchester, E. W., Schilder, B. M., Robinson, K. R., Curtis, S. W., Skene, N., Leslie, E. J., & Cotney, J. L. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.18.633396 · Cited by 10 · see citing works
Naot, D., Wilson, L. C., Allgrove, J., Adviento, E., Piec, I., Musson, D. S., Cundy, T., & Calder, A. D. (2019) · Bone · doi:10.1016/j.bone.2019.115098 · Cited by 8 · see citing works
Brommage, R., Liu, J., & Powell, D. R. (2023) · Bone Research · doi:10.1038/s41413-022-00242-9 · Cited by 8 · see citing works
“These observations are consistent with the excessively wide proximal tibiae and distal femurs previously observed in Sfrp4 KO mice.(9,20) 0 12 24 36 48”
BackgroundResultInfluentialSelf-citationMicroCT analyses of mouse femoral neck architecture
Brommage, R., Jeter-Jones, S. L., Xiong, W., & Liu, J. (2019) · Bone · doi:10.1016/j.bone.2019.115040 · Cited by 8 · see citing works
Self-citationHenning, P., Movérare‐Skrtic, S., Westerlund, A., de Souza, P. P. C., Marcelino, T. F., Nilsson, K. H., Shahawy, M. E., Ohlsson, C., & Lerner, U. H. (2021) · Journal of Inflammation Research · doi:10.2147/jir.s323435 · Cited by 8 · see citing works
Choi, R. B., Hoggatt, A. M., Horan, D. J., Rogers, E. Z., Hong, J. M., & Robling, A. G. (2022) · Aging and Disease · doi:10.14336/ad.2022.0315 · Cited by 7 · see citing works
“As Wnt signaling in bone often exhibits envelope-specific effects [25, 26] which are poorly understood, other Wnt-targeted combination approaches might be available that preferentially enhance cortical effects, thus providing “designer” therapies based on the envelope to be affected [9].”
BackgroundShi, F., Yuan, G., Wu, Z., Luo, Z., Chen, Z., Liu, Q., Li, N., & Xu, R. (2025) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2025.01.010 · Cited by 8 · see citing works
Ohlsson, C., Farman, H. H., Gustafsson, K. L., Wu, J., Henning, P., Windahl, S. H., Sjögren, K., Gustafsson, J.-Α., Movérare‐Skrtic, S., & Lagerquist, M. K. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00018.2020 · Cited by 7 · see citing works
Enfermedad de Pyle: un modelo humano de homeostasis corticotrabecular diferenciada
Arboleya, L. R., Queiró, R., Alpéri, M., Lorenzo, J. A., & Ballina, J. (2018) · Reumatología Clínica · doi:10.1016/j.reuma.2018.01.002 · Cited by 7 · see citing works
Xu, Y., Xie, Z., Gu, S., Zhao, X., Zhao, D., Wu, Z., Wang, J., Xu, T., Xu, R., Feng, Z., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06798-4 · Cited by 8 · see citing works
Untapped opportunities for rare disease gene discovery in India
Girisha, K. M., Pande, S., Dalal, A. B., & Phadke, S. R. (2020) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61866 · Cited by 6 · see citing works
“Majority publications relied on international collaborations for studies on cellular and animal models (Kiper et al., 2016; Szenker-Ravi et al., 2018) and a few of them were focussed only on strong clinical and genomic evidences (Girisha, Shukla, et al.”
BackgroundSelf-citationCraniofacial, dental, and molecular features of Pyle disease in a South African child
Chetty, M., Roomaney, I. A., Oosterwyk, C., Manyisa, N. R., Bope, C. D., Agenbag, G., & Wonkam, A. (2022) · BDJ Open · doi:10.1038/s41405-022-00120-w · Cited by 6 · see citing works
“Recently the secreted frizzled-related protein 4 (sFRP4), (606570) on chromosome 7p14 has been identified as a causative gene [7, 11, 12].”
BackgroundMethodInfluentialXu, Y., Sun, J., Yang, X., Yu, Y., Mai, H., & Li, Z. (2017) · Journal of Oral and Maxillofacial Surgery · doi:10.1016/j.joms.2017.03.016 · Cited by 6 · see citing works
Signaling in Osteoblast Differentiation
Hayashi, M., Ono, T., & Nakashima, T. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11182-1 · Cited by 6 · see citing works
Wang, X., Xin, H., Ning, X., Zhang, Y., Liu, F., Zhang, Z., Jia, X., Guo, W., Hong, Y., & Sui, W. (2022) · Biomedical Materials · doi:10.1088/1748-605x/ac61fb · Cited by 5 · see citing works
“A recent study showed that sfrp4, an inhibitor of the Wnt pathway, can activate the noncanonical Wnt pathway when it is inhibited, thereby negatively regulating the canonical Wnt pathway [22].”
Sclerostin Inhibition in the Treatment of Osteoporosis
Baron, R., Gori, F., & Leder, B. Z. (2020) · Contemporary Endocrinology · doi:10.1007/978-3-319-69287-6_19 · Cited by 5 · see citing works
Self-citationGuirado, E., Villani, C., Petho, A., Chen, Y., Maienschein‐Cline, M., Lei, Z., Los, N. S., & George, A. (2023) · International Journal of Oral Science · doi:10.1038/s41368-022-00214-z · Cited by 5 · see citing works
“sFRP-4 has been associated with Wnt Family Member 5A (WNT5A) expression and noncanonical Wnt signaling pathway activity, as well as, activation of bone morphogenic protein (BMP) signaling and sclerostin (SOST) gene expression, contributing to decreased bone formation.(24) Indeed, patients with XLH are reported to have…”
BackgroundPyle's disease: A human model of differentiated cortical and trabecular homeostasis
Arboleya, L. R., Queiró, R., Alpéri, M., Lorenzo, J. A., & Ballina, J. (2019) · Reumatología Clínica (English Edition) · doi:10.1016/j.reumae.2018.01.005 · Cited by 5 · see citing works
Aging Alters mRNA Processing in the Mouse Ovary
Vo, K., Pei, G. J., Thiyagarajan, R., Fields, P. E., & Rumi, M. A. K. (2025) · Cells · doi:10.3390/cells14130996 · Cited by 4 · see citing works
Shan, L., Liao, X., Yang, X., Zhu, E., Yuan, H., Zhou, J., Li, X., & Wang, B. (2024) · Genes & Diseases · doi:10.1016/j.gendis.2024.101209 · Cited by 4 · see citing works
A review of skeletal dysplasia research in India
Uttarilli, A., Shah, H. H., Shukla, A., & Girisha, K. M. (2018) · Journal of Postgraduate Medicine · doi:10.4103/jpgm.jpgm_527_17 · Cited by 4 · see citing works
“[62] have showed that a homozygous frameshift variation in sFRP4 gene was found to be associated with the Pyle’s disease in humans.”
Self-citation
- Authors
- Simsek Kiper, P. O., Saito, H., Gori, F., Unger, S., Hesse, E., Yamana, K., Kiviranta, R., Solban, N., Liu, J., Brommage, R., Boduroglu, K., Bonafé, L., Campos-Xavier, B., Dikoglu, E., Eastell, R., Gossiel, F., Harshman, K., Nishimura, G., Girisha, K. M., Stevenson, B. J., Takita, H., Rivolta, C., Superti-Furga, A., & Baron, R.
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2016-06-30
- Volume
- 374
- Issue
- 26
- Pages
- 2553-2562
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5070790
- OpenAlex
- W2475138245
- Cited by
- 151
- References
- 37
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 10 · 2023: 11 · 2022: 13 · 2021: 18 · 2020: 18 · 2019: 22 · 2018: 21 · 2017: 16 · 2016: 1
- FWCI
- 24.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IRIS (submittedVersion)
- Hacettepe University Institutional Repository (hacettepe.edu.tr) (submittedVersion, other-oa)
- SERVAL (Université de Lausanne) (submittedVersion)
- edoc (University of Basel)
- Funders
- Amgen
- National Institute for Health and Care Research (NF-SI-0513-10073)
- Türkiye Bilimsel ve Teknolojik Araştırma Kurumu
- Fondation Leenaards
- National Institutes of Health
- Medical Research Council (MR/K006312/1)
- Japan Society for the Promotion of Science
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR064724)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- SFRP4, cortical bone thinning, trabecular bone, Wnt signaling, BMP signaling, sclerostin, bone homeostasis, hereditary bone disease, knockout mouse models, non-vertebral fractures
- MeSH terms
- Secreted Frizzled-Related Proteins, Adolescent, Animals, Bone and Bones, Child, Preschool, Disease Models, Animal, Female, Homeostasis, Humans, Male, Middle Aged, Osteochondrodysplasias, Proto-Oncogene Proteins, Signal Transduction, Biomarkers, Bone Density, Bone Remodeling, Gene Deletion, Sequence Analysis, DNA, Mice, Knockout, Bone Morphogenetic Proteins, Wnt Proteins, Mice
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