Abstract
Osteoporosis is associated with delayed and/or reduced fracture healing. As cervus and cucumis are the traditional Chinese treatments for rheumatoid arthritis, we investigated the effect of supplementation of these peptides (CCP) on bone fracture healing in ovariectomized (OVX) osteoporotic rats in vitro and in vivo. CCP enhanced osteoblast proliferation and increased alkaline phosphatase activity, matrix mineralization, and expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 4 (BMP4), and osteopontin. In vivo, female Sprague-Dawley rats underwent ovariectomy and the right femora were fractured and fixed by intramedullary nailing 3 months later. Rats received intraperitoneal injections of either CCP (1.67 mg/kg) or physiological saline every day for 30 days. Fracture healing and callus formation were evaluated by radiography, micro-CT, biomechanical testing, and histology. At 12 weeks after fracture, calluses in CCP-treated bones showed significantly higher torsional strength and greater stiffness than control-treated bones. Bones in CCP-treated rats reunified and were thoroughly remodeled, while two saline-treated rats showed no bone union and incomplete remodeling. Taken together, these results indicate that use of CCP after fracture in osteoporotic rats accelerates mineralization and osteogenesis and improves fracture healing.
Highlights
Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bony tissue, which leads to bone fragility and increased risk of fracture [1] of the hip, spine, and wrist because of brittle bones
Osteoporosis affects more than 75% of the population in Europe, the United States, and Japan [2] and has been predicted to cause more than 50% of hip fractures in Asia by the year 2050 [3]
While osteoporosis therapies are designed to boost bone mass and prevent further bone loss, the most common therapy, bisphosphonates (BPs), may have negative effects on healing; animal and clinical studies have found that BPs delay fracture union [6,7,8]
Summary
Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bony tissue, which leads to bone fragility and increased risk of fracture [1] of the hip, spine, and wrist because of brittle bones. According to the US National Institutes of Health, an estimated 10 million Americans have osteoporosis and a further 18 million have low bone mass, placing them at increased risk for the disease. While osteoporosis therapies are designed to boost bone mass and prevent further bone loss, the most common therapy, bisphosphonates (BPs), may have negative effects on healing; animal and clinical studies have found that BPs delay fracture union [6,7,8]
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