Search

Low-energy fractures are frequent complications in type 1 diabetes mellitus patients (T1DM). Modifications of bone intrinsic composition might be a potential cause of fragility observed in diabetic subjects. Advanced glycation end products (AGEs) were found in numerous connective tissues from T1DM patients. However, whether AGEs are present at high levels in bone matrix from diabetic subjects is unknown. Moreover, whether elevated AGEs in the bone matrix impair mineralization has not been addressed in humans. The purposes of this study were 1) to determine whether bone matrix from fracturing and nonfracturing T1DM contained more AGEs than bone from healthy patients (CTL), and 2) to compare the degree of mineralization of bone and hardness between fracturing and nonfracturing T1DM versus CTL. We analyzed iliac crest bone biopsies from 5 fracturing T1DM patients, 5 nonfracturing T1DM patients, and 5 healthy subjects, all age-and sex-matched. AGEs (pentosidine) in bone matrix was measured by high-performance liquid chromatography separately in trabecular and cortical bone. The degree of mineralization of bone (DMB) was assessed by digitized microradiography, and mechanical properties by micro-and nanohardness tests. Trabecular bone from fracturing T1DM exhibited significantly higher levels of pentosidine than CTL (p = 0.04) and was more mineralized than nonfracturing T1DM (p = 0.04) and CTL (p = 0.04). Trabecular bone was not significantly different in pentosidine between nonfracturing T1DM and CTL. Cortical bone from nonfracturing T1DM was not significantly different from CTL. Positive correlations were found between HbA1c and pentosidine (r' = 0.79, p < 0.003) and between HbA1c and DMB (r' = 0.64, p < 0.02). Both modifications could lead to less flexible bone (reduced modulus of elasticity) and a tendency toward low-energy fractures in T1DM patients. [ABSTRACT FROM AUTHOR]

Though osteonecrosis of the jaw (ONJ) is temporally-associated with the use of nitrogen-containing bisphosphonates (N-BPs), a cause-and-effect relationship has not yet been established. We hypothesize that ONJ is a two-stage process in which: (1) risk factors initiate pathologic processes in the oral cavity that lead to a supranormal rate of hard tissue necrosis; and (2) powerful antiresorptives reduce the rate of removal of necrotic bone sufficiently to allow its net accumulation in the jaw. To test this hypothesis, we used the rice rat model of periodontitis. At age 28 days, rats ( n = 15/group) were placed on a high-sucrose and casein diet to exacerbate the development of periodontitis. Animals were injected subcutaneously (SC) biweekly with vehicle or alendronate (ALN, 15 µg/kg), or IV once monthly with vehicle, a low dose (LD) of zoledronic acid (ZOL), or a high dose (HD) of ZOL and sacrificed after 6, 12, 18, and 24 weeks. Mandibles and maxillae were analyzed to determine the effects on the: (1) progression of periodontitis; (2) integrity of alveolar bone; (3) status of bone resorption and formation; (4) vascularity; and (5) osteocyte viability. We found that only HD-ZOL induced ONJ-like lesions in mandibles of rice rats after 18 and 24 weeks of treatment. These lesions were characterized by areas of exposed necrotic alveolar bone, osteolysis, a honeycomb-like appearance of the alveolar bone, presence of bacterial colonies, and periodontal tissue destruction. In addition, inhibition of bone formation, a paradoxical abolition of the antiresorptive effect of only HD-ZOL, increased osteocyte necrosis/apoptosis, and decreased blood vessel number were found after 18 and/or 24 weeks. Our study suggests that only HD-ZOL exacerbates the inflammatory response and periodontal tissue damage in rice rats, inducing bone lesions that resemble ONJ. © 2012 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]