Bone chemistry of osteoporosis revealed by synchrotron infrared microspectroscopy

Abstract

Osteoporosis is a disease characterized by compromised bone strength predisposing to an increased risk of fracture. Reduced bone density is a well-known feature of osteoporosis, yet little is known about the changes in the chemical composition of bone or the impact of such chemical changes on fracture risks. A quantitative study of both the organic and inorganic components of bone is important for understanding the disease mechanism and facilitating treatment strategies.;Like post-menopausal women, ovariectomized cynomolgus monkeys ( Macaca fascicularis) experience accelerated loss of bone mass. Treatment of ovariectomized monkeys with nandrolone decanoate results in an increase in bone mass to levels comparable to those in intact animals. Using ovariectomized cynomolgus monkeys as a model for osteoporosis, we examined the chemical changes in both trabecular and cortical bone as a function of time after ovariectomy and nandrolone treatment. Fluorochrome labels were used to identify regions of bone remodeled 1 year (calcein) and 2 years (alizarin complexone) after ovariectomy and synchrotron infrared microspectroscopy was used to determine protein and mineral content and composition in these particular regions of bone.;Results demonstrate that ovariectomy does not affect the average mineralization levels (as defined by the phosphate/protein ratio) of cortical or trabecular bone. However, the rate of new bone mineralization after ovariectomy increases in cortical bone, whereas it remains unchanged in trabecular bone. Ovariectomy reduces the average carbonate accumulation in cortical bone. Although it does not affect the average trabecular bone accumulation, the rate at which carbonate accumulates in new trabecular bone is reduced after ovariectomy. The carbonate in hydroxyapatite experiences the same changes as the phosphate, while the labile carbonate decreases in both bone regions.;Acid phosphate, which is abundant in immature bone, increases after ovariectomy concomitantly with the changes in carbonate and mature-type collagen cross-links. The average collagen cross-linking of mature bone is not affected by ovariectomy, but it significantly increases in new trabecular bone and decreases in new cortical bone. Treatment of the ovariectomized monkeys with nandrolone decanoate, a drug that decreases bone resorption, reverses most of the chemical changes in the cortical bone to the levels of the ovary-intact controls, but has little effect on the trabecular bone.