2011
DOI: 10.14310/horm.2002.1308
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Targeting the osteoblast: approved and experimental anabolic agents for the treatment of osteoporosis

Abstract: targeting osteoblast may be the means of effectively improving both bone quality and mass, thus offering an intriguing alternative in the treatment of osteoporosis. Aside from injectable parathyroid hormone (PtH) and its novel preparations, PtH-related peptide (PtHrP), calcilytics, beta-adrenergic receptors, enhancement of Wnt signaling (mainly via sclerostin and Dickkopf-1 neutralization), regulation of low-density lipoprotein receptor-related protein (LPr) 5/osteoblast axis, activin, IGF-1, and bone morphoge… Show more

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Cited by 26 publications
(15 citation statements)
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“…In summary, Lepr(-/-) mice showed both damaged osteoblastic bone formation and osteoclastic bone resorption that would result in low-turnover osteopathia, consistent with the low-turnover osteopenia observed in diabetic animals [45]. Since HPTHrP-(1-84) administration resulted in elevated extracellular calcium levels through increasing of renal calcium transport and osteoblastic bone formation without affecting bone resorption [10], we infer that the differences between half-life and functions of diverse PTHrP sequences might explain these diverse findings.…”
Section: Discussionsupporting
confidence: 77%
“…In summary, Lepr(-/-) mice showed both damaged osteoblastic bone formation and osteoclastic bone resorption that would result in low-turnover osteopathia, consistent with the low-turnover osteopenia observed in diabetic animals [45]. Since HPTHrP-(1-84) administration resulted in elevated extracellular calcium levels through increasing of renal calcium transport and osteoblastic bone formation without affecting bone resorption [10], we infer that the differences between half-life and functions of diverse PTHrP sequences might explain these diverse findings.…”
Section: Discussionsupporting
confidence: 77%
“…However, both PTH1-34) and PTH1-84) induce an excessive bone remodeling and carry the Bblack box^label of a 2-year prescription because of the long-term risk of osteosarcoma in preclinical studies in rats. When compared to the administration of PTH(1-34) or PTH(1-84), calcilytic drugs present advantages, namely, the ability to be orally bioavailable and modulate secretion of endogenous PTH, which ensures that PTH serum levels do not increase beyond the physiological range [88]. Thus, the main desirable characteristics present in calcilytic compounds are the ability to transiently increase PTH secretion, in order to obtain the anabolic effects of the hormone and lead to bone formation, drug specificity to the CaSR, and oral administration.…”
Section: Calcilytics: Effects On Bonementioning
confidence: 99%
“…Indeed, systemic PTH caused a decrease in serum phosphate levels only in wild type females, not in Ramp2 heterozygous females. While the long-term physiologic consequences of this are unclear, the established therapeutic roles of PTH and PTHrP in diseases like osteoporosis and cancer underscore the importance of understanding consequences of the RAMP2-PTH1R interaction in various organ systems in vivo [2730]. …”
Section: Discussionmentioning
confidence: 99%