Synthetic Bone Mineral (SBM) for Osteoporosis Therapy: Part 1 - Prevention of Bone Loss from Mineral Deficiency

摘要

Osteoporosis is a 'silent' disease characterized by thinning cortical bone and disorganized trabecular architecture causing bone fragility leading to fracture. Osteoporosis results when the rate of bone resorption far exceeds the rate of bone formation. Current pharmaceutical interventions (estrogen therapy, bisphosphonate-based drugs) focus on inhibiting bone resorption. However, some of these therapies have serious side effects (e.g., cancer risk from estrogen therapy; osteonecrosis of the jaw and delayed fracture healing from bisphosphonate-based drugs). The long term objective of the study was to develop a novel material for potential osteoporosis therapy, prevention and fracture repair. This novel material MZF-CaP or synthetic bone mineral, SBM) incorporates Mg, Zn and F ions in a calcium phosphate matrix. Separately, magnesium (Mg), zinc (Zn) and fluoride (F) ions have been associated with biomineralization and osteoporosis therapy in human and in animals. MZF-CaP or SBM was prepared by a modified hydrolysis method previously described and characterized using x-ray diffraction, FT-IR spectroscopy, inductive coupled plasma and dissolution in acidic buffer. Separately, male and female Sprague-Dawley rats were randomly assigned to the following groups depending on the diet: GA: normal on basic diets; GB: on mineral deficient diets (md); GC: on md + Mg-CaP; GD: on md + Zn-CaP; GE: md+F-CaP; and GF: md+MZF-CaP. The rats were sacrificed after 3 months and the femur bones separated, cleaned of extraneous soft tissues and stored until needed for analyses. Femur bones were analyzed using microradiography (Faxitron), scanning electron microscopy (SEM) and microCT. Results: SEM, Faxitron and microCT analyses showed thinning of cortical bone and disorganized trabecular bone architecture for osteoporotic rats on mineral deficient diet (GB) and prevention of bone loss in rats receiving the supplemented diets (GC,GD,GE,GF). Conclusion: These results indicate that the novel material, MZF-CaP or SBM had a potential for osteoporosis therapy and prevention. Studies to demonstrate the use of SBM in reversing (recovering) bone loss are in progress.