A prospective study of bone loss and turnover after allogeneic bone marrowtransplantation: effect of calcium supplementation with or without calcitonin

Transplantation of solid organs including heart, kidney, and liver is assoc iated with rapid bone loss and increased rate of fracture; data on bone mar row transplantation recipients (BMT) are scarce. The purpose of the present study was to examine the magnitude, timing, and mechanism of bone loss fol lowing allogeneic BMT, and to study whether bone loss can be prevented by c alcium with or without calcitonin. Sixty-nine patients undergoing allogenei c BMT for malignant blood diseases were enrolled into the study. Forty-four (22 women, 22 men) completed 6 months, and 36 patients 1 year follow-up. T hey were randomized to receive either no additional treatment (n = 22), or oral calcium Ig twice daily for 12 months (n = 12) or the same dose of calc ium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months (n = 10). Bone mineral density (BMD) at the lumbar spi ne and three femoral sites (femoral neck, trochanter, Ward's triangle) was measured by dual-energy X-ray absorptiometry (DXA). Bone turnover rate was followed with markers of bone formation and resorption (serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal (PICP) an d aminoterminal propeptide (PINP), serum type I collagen carboxyterminal te lopeptide (ICTP)). Serum testosterone was assayed in men. Calcium with or w ithout calcitonin had no effect on bone loss or bone markers; consequently the three study groups were combined. During the first 6 post-transplant mo nths BMD decreased by 5.7% in the lumbar spine and by 6.9% to 8.7% in the t hree femoral sites (P < 0.0001 for all); no significant further decline occ ured between 6 and 12 months. Four out of 25 assessable patients experience d vertebral compression fractures. Markers of bone formation reduced: B-ALB by 20% at 3 weeks (P = 0.027), PICP by 40% (P < 0.0001) and PINP by 63% at 6 weeks (P < 0.0001), with a return to baseline by 6 months. The marker of bone resorption, serum ICTP was above normal throughout the whole observat ion period, with a peak at 6 weeks (77% above baseline, P < 0.0001). In mal e patients serum testosterone decreased reaching a nadir (57% below baselin e) at 6 weeks (P = 0.0003). In conclusion, significant bone loss occurs aft er BMT. It results from imbalance between reduced bone formation and increa sed bone resorption; hypogonadism may be a contributing factor in men. Bone loss can not be prevented by calcium with or without calcitonin.