Bisphosphonates do not alter the rate of secondary mineralization

Bisphosphonates function to reduce bone turnover, which consequently increases the mean degree of tissue mineralization at an organ level. However, it is not clear if bisphosphonates alter the length of time required for an individual bone-modeling unit (BMU) to fully mineralize. We have recently demonstrated that it takes ~ 350 days (d) for normal, untreated cortical bone to fully mineralize. The aim of this study was to determine the rate at which newly formed trabecular BMUs become fully mineralized in rabbits treated for up to 414 d with clinical doses of either risedronate (RIS) or alendronate (ALN). Thirty-six, 4-month old virgin female New Zealand white rabbits were allocated to RIS (n = 12; 2.4 μg/kg body weight), ALN (n = 12; 2.4 μg/kg body weight), or volume-matched saline controls (CON; n = 12). Fluorochrome labels were administered at specific time intervals to quantify the rate and level of mineralization of trabecular bone from the femoral neck (FN) by Fourier transform infrared microspectroscopy (FTIRM). The organic (collagen) and inorganic (phosphate and carbonate) IR spectral characteristics of trabecular bone from undecalcified 4 micron thick tissue sections were quantified from fluorescently labels regions that had mineralized for 1, 8, 18, 35, 70, 105, 140, 210, 280, and 385 d (4 rabbits per time point and treatment group). All groups exhibited a rapid increase in mineralization over the first 18 days, the period of primary mineralization, with no significant differences between treatments. Mineralization continued to increase, at a slower rate up, to 385 days (secondary mineralization), and was not different among treatments. There were no significant differences between treatments for the rate of mineralization within an individual BMU; however, ALN and RIS both increased global tissue mineralization as demonstrated by areal bone mineral density from DXA. We conclude that increases in tissue mineralization that occur following a period of bisphosphonate treatment is a function of the suppressed rate of remodeling that allows for a greater number of BMUs to obtain a greater degree of mineralization.

Research highlights► Rate of trabecular mineralization increased rapidly within 18 days, with no significant differences between risedronate, alendronate and placebo controls. ► Mineralization increased at a slower rate up to 385 days with no significant differences between risedronate, alendronate and placebo controls. ► Increased BMD in bisphosphonate treated animals is caused by more fully mineralized BMU's. ► Bone tissue treated with bisphosphonates was not hypermineralized.