Histomorphometric analysis reveals reduced bone mass and bone formation in patients with quiescent Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is associated with an increased prevalence of osteoporosis, but the pathogenesis of this bone loss is only partly understood. We assessed bone structure and remodeling at the tissue level in patients with quiescent CD. We also investigated the roles of osteocyte density and apoptosis in CD-associated bone loss. METHODS: The study included 23 patients with quiescent CD; this was a subgroup of patients from a large randomized, double-blind, placebo-controlled, multicenter trial. We obtained transiliac bone biopsy samples and performed histomorphometric analysis. Results were compared with data from age- and sex-matched healthy individuals (controls). RESULTS: Trabecular bone volume was decreased among patients with CD compared with controls (18.90% vs 25.49%; P < .001). The low bone volume was characterized by decreased trabecular thickness (120.61 vs 151.42 µm; P < .01). Bone formation and resorption were reduced, as indicated by a decreased mineral apposition rate (0.671 vs 0.746 µm/day; P < .01) and a low osteoclast number and surface area compared with controls and published values, respectively. In trabecular bone of patients with CD, osteocyte density and apoptosis were normal. The percentage of empty lacunae among patients was higher than that of published values in controls. CONCLUSIONS: In adult patients with quiescent CD, bone histomorphometric analysis revealed a reduction in bone mass that was characterized by trabecular thinning. The CD-associated bone loss was caused by reduced bone formation, possibly as a consequence of decreased osteocyte viability in the patients' past.

Effect of long-term growth hormone treatment on bone mass and bone metabolism in growth hormone-deficient men.

UNLABELLED: Long-term GH treatment in GH-deficient men resulted in a continuous increase in bone turnover as shown by histomorphometry. BMD continuously increased in all regions of interest, but more in the regions with predominantly cortical bone. INTRODUCTION: Adults with growth hormone (GH) deficiency have reduced rates of bone turnover and subnormal BMD. GH treatment is effective in enhancing bone turnover as shown by biochemical markers and bone histomorphometric studies. However, it is uncertain whether long-term treatment will result in higher bone mass. In this study, we present BMD and histomorphometric data on 5 years of GH treatment in GH-deficient men. MATERIALS AND METHODS: Thirty-eight adult men with childhood onset GH deficiency (20-35 years) were included in the study. Twenty-six of these had multiple pituitary hormone deficiencies and were on stable conventional hormone replacement. BMC (total body) and BMD (lumbar spine and hip) were measured before and after 1, 2, 3, 4, and 5 years of treatment. BMD in various regions of the total body was calculated by computer software (head, trunk, arms, and legs). Transiliac bone biopsies were obtained before and after 1 and 5 years of GH treatment. RESULTS: Total body BMC increased 18% after 5 years of treatment. This increase was observed in all regions of interest: head, 13.7%; trunk, 27.8%; arms, 24.4%; legs, 13.8%. BMD also increased in all separately measured regions: lumbar spine, 9%; femoral neck, 11%; femoral trochanter, 16%. Lumbar spine area significantly increased (p=0.0002). Histomorphometric data showed increased osteoid surface (p<0.02), osteoid volume (p<0.01), and activation frequency (p<0.006), but trabecular bone volume did not increase significantly. Qualitative assessment of the cortical bone showed endosteal and periosteal bone formation. CONCLUSIONS: In conclusion, GH considerably increases BMC after long-term treatment. The combination of BMD and histomorphometric data suggests that GH has a greater effect on cortical than on trabecular bone.

Effect of raloxifene treatment on osteocyte apoptosis in postmenopausal women.

Increased osteocyte apoptosis, as the result of estrogen deficiency, could play a role in the decrease of bone mass and bone strength seen in postmenopausal osteoporosis. We investigated whether treatment with raloxifene of postmenopausal women with osteoporosis affects osteocyte apoptosis. Transiliac bone biopsies were obtained from 26 osteoporotic women at baseline and after 2 years of treatment with placebo or raloxifene. Immunohistochemical detection of cleaved caspase-3 was performed on sections from nondecalcified bone biopsies to visualize apoptosis. In the trabecular bone total osteocytes, positively stained osteocytes and empty lacunae were counted and percent positive cells and percent empty lacunae determined. Statistical evaluation was performed by Wilcoxon's paired t-test and Spearman's rank correlations. There was no significant difference in percentage positive osteocytes between baseline and follow-up biopsies in both the placebo and the raloxifene groups. The percentage empty lacunae increased significantly in the placebo group (11.20 +/- 1.43 vs. 9.00 +/- 2.25, P = 0.014) but not in the raloxifene group. At baseline in both groups combined, there was a negative correlation between indices of bone remodeling and the percentage positive osteocytes (bone formation rate/bone volume r = -0.67, P = 0.001). We found no direct evidence for an effect of raloxifene treatment on osteocyte apoptosis, but small effects of raloxifene treatment cannot be excluded. The percent of apoptotic osteocytes was dependent on the level of bone remodeling in an individual.