Interplay between mineral crystallinity and mineral accumulation in health and postmenopausal osteoporosis

Osteoporosis is characterized by an imbalance between bone formation and resorption rates, resulting in bone loss. For ethical reasons, effects of antiosteoporosis drugs are compared against patients receiving vitamin D and calcium supplementation which is a mild antiresorptive regimen. Bone formation may be resolved into two phases: the initial formation of mineral crystals (primary nucleation) and the subsequent mineral accumulation (secondary nucleation and mineral growth) on them. In this study, we used Raman microspectroscopic analysis of iliac crest biopsies from healthy females (N = 108), postmenopausal osteoporosis patients receiving vitamin D and calcium supplementation (PMOP-S; N = 66), and treatment-naïve postmenopausal osteoporosis patients (PMOP-TN; N = 12) to test the hypothesis that at forming trabecular surfaces, mineral maturity / crystallinity of the youngest crystallites associates with the amount of subsequent mineral accumulation. The surfaces of analysis were chosen based on the presence of fluorescent double labels, defining three distinct tissue ages. The results indicated that when adjusted for age and tissue age, there were no differences in amount of mineral formed between healthy females and either PMOP-S or PMOP-TN, while both PMOP-S and PMOP-TN had larger crystallites compared to healthy females. Moreover, significant differences existed between PMOP-S and PMOP-TN in size of initial crystals formed as well as rate of mineral accumulation and maturation. These findings suggest an additional mechanism that may contribute to the decreased mineral content evident in PMOP, and provide a potential target for the development of new interventions. STATEMENT OF SIGNIFICANCE: We used Raman microspectroscopic analysis of iliac crest biopsies from healthy females and postmenopausal osteoporosis patients (PMOP) receiving placebo to test the hypothesis that at forming trabecular surfaces, mineral maturity / crystallinity (MMC) of the youngest crystallites associates with the amount of subsequent mineral accumulation. This can affect bone mechanical properties as larger crystallites have been shown to result in compromised mechanical attributes; and larger crystallites grow slower compared to smaller ones. The results of the present analysis indicate that increased MMC of the youngest formed mineral may contribute to the bone mineral loss evident in PMOP and the accompanying increased fracture risk independently of bone turnover rate.