A Randomized, Double-Blind, Placebo Controlled Proof-of-Concept Study Investigating the Safety and Efficacy of ZT-031 on Hip Fracture Healing in Men and Postmenopausal Women With Intertrochanteric Fracture of the Hip

The purpose of this research study is to test if an experimental drug called ZT-031 can help men over 30 years or post-menopausal women over 55 years of age with certain types of hip fracture to heal better or faster following surgery and to determine if ZT-031 is safe for patients with fractures. To be allowed in the study you have to have a type of hip fracture that requires surgery that is being studied (intertrochanteric fracture). You must also otherwise be in good health, with no serious diseases such as cancer, neurologic disease, other bone disease, liver, heart or kidney disease. You must be able to inject yourself every day with the study medication using an injection pen, like that used for insulin injections.

开始日期2008-12-01

申办/合作机构

Azelon Pharmaceuticals, Inc.

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项与 Ostabolin(Azelon Pharmaceuticals, Inc.) 相关的文献（医药）

2023-07-01·Connective tissue research

β-Arrestin 2 knockout prevents bone loss in response to continuous parathyroid hormone stimulation in male and female mice.

Article

作者: Mitchell, Jane ; Li Feng, Gilberto ; Grynpas, Marc D

BACKGROUNDβ-Arrestin 2 (β-arr2) binds activated parathyroid hormone (PTH) receptors stimulating internalization. PTH stimulates both anabolic and catabolic effect on bone depending on the way it is administered. Intermittent PTH stimulation increases trabecular bone formation in mice, but this is decreased in mice lacking β-arr 2, suggesting a role for β-arr 2 in the anabolic effects of PTH. The role of β-arr 2 in the catabolic effects of continuous PTH (cPTH) treatment is not known.OBJECTIVETo assess the effects of cPTH administration on bone in mice lacking β-arr 2 compared to wild-type (WT).METHODSGroups of male and female WT or β-arr2 knockout (KO) mice were administered either PTH or phosphate-buffered saline by osmotic pumps for 2 weeks. Following treatment, serum calcium and phosphate levels were measured, bone structure and mineral density were measured by microcomputed tomography, and bone cells measured by static and dynamic histomorphometry.RESULTSβ-arr2 KO had no effects on skeletal development in mice of either sex. PTH treatment caused hypercalcemia and hypophosphatemia and decreased trabecular and cortical bone only in male WT mice. β-arr2 KO in male mice completely abrogated the effects of PTH on bone, while in female β-arr2 KO mice, PTH treatment increased trabecular bone with no effects on cortical bone.CONCLUSIONSThese results demonstrate a profound sex effect on skeletal responses to cPTH treatment, suggesting a protective effect of estrogen on bone loss. β-arr2 plays a role in restraining the anabolic effects of PTH in both male and female mice.

2022-07-01·Journal of Endocrinology

Increased osteoblast GαS level determines bone response to hyperparathyroidism in female mice

Article

作者: Mitchell, Jane ; Sugamori, Kim S ; Zhang, Lucia ; Lee, Kathy K ; Grynpas, Marc D

GS, the stimulatory heterotrimeric G protein, is an essential regulator of osteogenesis and bone turnover. To determine if increasing GαS in osteoblasts alters bone responses to hyperparathyroidism, we used a transgenic mouse line overexpressing GαS in osteoblasts (GS-Tg mice). Primary osteoblasts from GS-Tg mice showed increased basal and parathyroid hormone (PTH)-stimulated cAMP and greater responses to PTH than cells from WT mice. Skeletal responses to 2-week continuous PTH administration (cPTH) in female mice resulted in trabecular bone loss in WT mice but 74% and 34% increase in trabecular bone mass in long bones and vertebrae, respectively, in GS-Tg mice. Vertebral biomechanical strength was compromised by cPTH treatment in WT mice but not in GS-Tg. Increased peritrabecular fibrosis was greatly increased by cPTH in Gs-Tg compared to WT mice and corresponded with greater increases in Wnt pathway proteins in trabecular bone. Cortical bone responded negatively to cPTH in WT and Gs-Tg mice with large increases in porosity, decreased cortical thickness and compromised biomechanical properties. These results demonstrate that hyperparathyroidism can increase trabecular bone when GS expression and cAMP stimulation in osteoblasts are increased but this is not the case in cortical bone where increased GS expression exacerbates cortical bone loss.

2019-08-01·Journal of Bone and Mineral Research

Parathyroid Hormone Remodels Bone Transitional Vessels and the Leptin Receptor-Positive Pericyte Network in Mice

Article

作者: He, Zhiguo ; Picot, Tiphanie ; Campos, Lydia ; Aanei, Carmen-Mariana ; Lafage-Proust, Marie-Hélène ; Caire, Robin ; Roche, Bernard ; Vico, Laurence ; Malaval, Luc ; Thomas, Mireille

ABSTRACTIntermittent parathyroid hormone (iPTH) is anti-osteoporotic and affects bone vessels. Transitional capillaries close to the bone surface, which express both endomucin (Edm) and CD31, bear leptin receptor-expressing (LepR) perivascular cells that may differentiate into osteoblasts. Increased numbers of type H endothelial cells (THEC; ie, Edmhi/CD31hi cells assessed by flow cytometry, FACS) are associated with higher bone formation in young mice. We hypothesized that iPTH administration impacts transitional vessels by expanding THECs. Four-month-old C57/Bl6J female mice were injected with PTH 1–84 (100 μg/kg/d) or saline (CT) for 7 or 14 days. We quantified LepR+, CD31+, Edm+ cells and THECs by FACS in hindlimb bone marrow, and Edm/LepR double immunolabelings on tibia cryosections. Additionally, we analyzed bone mRNA expression of 87 angiogenesis-related genes in mice treated with either intermittent or continuous PTH (iPTH/cPTH) or saline (CT) for 7, 14, and 28 days. iPTH dramatically decreased the percentage of THECs by 78% and 90% at days 7 and 14, respectively, and of LepR+ cells at day 14 (–46%) versus CT. Immunolabeling quantification showed that the intracortical Edm+-vessel density increased at day 14 under iPTH. In the bone marrow, perivascular LepR+ cells, connected to each other via a dendrite network, were sparser under iPTH at day 14 (–58%) versus CT. iPTH decreased LepR+ cell coverage of transitional vessels only (–51%), whereas the number of LepR+ cells not attached to vessels increased in the endocortical area only (+ 49%). Transcriptomic analyses showed that iPTH consistently upregulated PEDF, Collagen-18α1, and TIMP-1 mRNA expression compared with CT and cPTH. Finally, iPTH increased immunolabeling of endostatin, a Collagen-18 domain that can be cleaved and become antiangiogenic, in both endocortical (79%) and peritrabecular transitional microvessels at day 14. Our results show that iPTH specifically remodels transitional vessels and suggest that it promotes LepR+ cell mobilization from these vessels close to the bone surface. © 2019 American Society for Bone and Mineral Research.Abstract

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
绝经期后骨质疏松	申请上市	加拿大	Azelon Pharmaceuticals, Inc.	-
髋部骨折	临床2期	美国	Azelon Pharmaceuticals, Inc.	2008-12-01
慢性肾病-矿物质和骨骼疾病	临床2期	-	Azelon Pharmaceuticals, Inc.	-
绝经期综合征	临床2期	-	Azelon Pharmaceuticals, Inc.	-