Pathogenesis Of Osteopenia Research Articles

Osteoporosis in hemochromatosis: iron excess, gonadal deficiency, or other factors?

To define the prevalence, severity, type and pathogenesis of osteopenia in idiopathic hemochromatosis. Prospective study conducted over 18 months. Tertiary care center. Twenty-two men with idiopathic hemochromatosis and 20 age-matched controls. There were 5 hypogonadal patients, 9 eugonadal nonvenesected patients, and 8 eugonadal venesected patients. All patients and controls were evaluated by spinal radiography, spinal and forearm bone mineral density estimations, dynamic skeletal histomorphometry, and serum biochemistry. Ten patients (45%; 95% CI, 24% to 68%) had osteoporosis as defined by spinal and forearm bone density measurements. Trabecular bone volumes were significantly reduced in the patients (the difference in means between patients and age-matched controls was 3.9%; CI, 1.3% to 6.7%). No patient had osteomalacia. Hypogonadal men had lower bone mass measurements than eugonadal men (radial bone density: beta coefficient = -20.5; CI, -29.2 to -11.8; trabecular bone volume: beta coefficient = -7.1; CI, -10.8 to -3.3). Osteoid and osteoblastic surfaces and bone formation rates were significantly greater in the eugonadal venesected compared with the eugonadal nonvenesected persons (P less than 0.05 for all measurements). A significant decrease in bone density is seen in idiopathic hemochromatosis, particularly when hypogonadism is present. Low serum free-testosterone concentrations rather than the calciotrophic hormones determine bone mass in this condition.

Diminished Bone Formation in Experimental Diabetes: Relationship to Osteoid Maturation and Mineralization

The pathogenesis of osteopenia in clinical diabetes remains uncertain. Thus, bone formation, mineralization, and resorption were measured over a 10-day period using double-tetracycline labeling of bone in control (C, N = 18), untreated diabetic (I-, N = 14), and insulin-treated diabetic (I+, N = 16) rats. Diabetes was induced by the intravenous (i.v.) injection of streptozotocin (STZ), 90 mg/kg, in citrate buffer. Bone and matrix (osteoid) formation and apposition were decreased by 50% from C values in I- rats (P less than 0.05), but were unchanged in I+ rats. Osteoid seam width and osteoid area were also less in I- (P less than 0.05), but similar in I+, when compared with C. In untreated diabetic rats that continued to actively form new bone, osteoid maturation and mineralization were not diminished when adjusted for the rate of bone formation. However, 5 of 14 untreated and 2 of 16 insulin-treated diabetic animals showed no uptake of tetracycline into bone (Chi-square, 8.54; P less than 0.05), suggesting a defect in mineralization in a subset of diabetic rats. Measurements of serum glucose, calcium, and phosphorus concentrations, of urinary excretion rates for glucose, calcium, and phosphorus, and of creatinine clearance failed to correlate with the changes in bone growth and histology observed. The results indicate heterogeneity in the response of bone in diabetes, and suggest that bone formation and osteoid volume are reduced early in the course of this disorder. These data in short-term diabetes support previous observations in both man and rat that indicate a state of low bone turnover in diabetes.