Previous studies have demonstrated the effects of sclerostin antibody (Scl-Ab) and parathyroid hormone (1-34, PTH) on healing in osteoporosis; however, reports about the combined effects of Scl-Ab plus PTH on osteoporosis are limited. This study was designed to investigate the impact of combined treatment with Scl-Ab and PTH on osteoporosis healing in ovariectomized (OVX) rats. After bilateral ovariectomy, 12 weeks were allowed to pass for the establishment of standard conditions for osteoporosis in animal models. The rats then randomly received a vehicle (control), Scl-Ab (25 mg/kg body weight, twice weekly), PTH (60 μg/kg, three times per week) or PTH plus Scl-Ab until death at 12 weeks. The blood and distal femurs of the rats were harvested for evaluation. The results of treatment for osteoporosis were evaluated by serum analysis, histology, microcomputed tomography (micro-CT) and biomechanical tests. Results from this study indicated that PTH + Scl-Ab had stronger effects on the prevention and treatment of osteoporosis than either of the monotherapies in OVX rats. The PTH + Scl-Ab produced the strongest effects on bone volume fraction (BV/TV), bone trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular spacing (Tb.Sp), bone mineral density (BMD) and strength of distal femurs and increased the levels of procollagen type I N‑terminal propeptide (PINP) and osteocalcin. In contrast, monotherapy with PTH or Scl-Ab showed no differences between treated groups in the assessment of the metaphysis of contralateral femurs by histology, serum, biomechanical tests and micro-CT. These results seem to indicate that Scl-Ab plus PTH has an additive effect on osteoporosis in OVX rats.
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http://dx.doi.org/10.1007/s00391-017-1219-1 | DOI Listing |
Bone Res
April 2023
Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood; and antiresorptive agents, the current standard of care, do not restore the weakened bone architecture. Herein, we reveal the diabetic bone signature in mice at the tissue, cell, and transcriptome levels and demonstrate that three FDA-approved bone-anabolic agents correct it. Diabetes decreased bone mineral density (BMD) and bone formation, damaged microarchitecture, increased porosity of cortical bone, and compromised bone strength.
View Article and Find Full Text PDFEMBO Mol Med
November 2022
Molecular Skeletal Biology Laboratory, Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Postmenopausal bone loss often leads to osteoporosis and fragility fractures. Bone mass can be increased by the first 34 amino acids of human parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), or by a monoclonal antibody against sclerostin (Scl-Ab). Here, we show that PTH and Scl-Ab reduce the expression of microRNA-19a and microRNA-19b (miR-19a/b) in bone.
View Article and Find Full Text PDFBone
January 2022
Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, United States of America; Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States of America. Electronic address:
X-linked hypophosphatemia (XLH) is caused by a loss-of-function mutation in the phosphate regulating gene with homology to endopeptidase located on the X chromosome (PHEX). Loss of functional PHEX results in elevated fibroblast growth factor 23 (FGF23), impaired phosphate reabsorption, and inhibited skeletal mineralization. Sclerostin, a protein produced primarily by osteocytes, suppresses bone formation by antagonizing canonical Wnt-signaling and is reported to be elevated in XLH patients.
View Article and Find Full Text PDFZ Gerontol Geriatr
March 2020
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, 109 W Xueyuan Road, 325027, Wenzhou, Zhejiang, China.
Osteoporotic bones heal more slowly and ineffectively than normal bones. A combination of antibodies against sclerosing protein (Scl-Ab), and parathyroid hormone 1-34 (PTH 1-34) may improve healing. A standard osteoporotic rat model was established 12 weeks after bilateral ovarian resection (OVX).
View Article and Find Full Text PDFBone
June 2019
Maine Medical Center Research Institute, Scarborough, ME, USA; University of Maine Graduate School of Biomedical Science and Engineering, Orono, ME, USA; Tufts University School of Medicine, Boston, MA, USA. Electronic address:
There is currently an unmet clinical need for improved treatments for skeletal diseases such as osteoporosis and cancer-induced bone disease. This is due in part to a paucity of novel targets and an incomplete understanding of the mechanisms of action for established therapies. We defined the effects of anabolic treatments on bone and the bone marrow adipocyte (BMA).
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