Chemotherapy-induced ovarian failure causes rapid bone loss in premenopausal breast cancer patients. Women older than 40 years are at particularly high risk. Clodronate significantly reduces this bone loss.

Objective: To study the effects of GH treatment for up to 42 months on bone mineral density (BMD) and bone turnover. Design and methods: BMD with dual energy X-ray absorptiometry, serum type I procollagen carboxyterminal propeptide (PICP), serum type I collagen carboxy-terminal telopeptide (ICTP) and serum IGF-I were assessed in 71 adults with GH deficiency. There were 44 men and 27 women, aged 20 to 59 (median 43) years. Thirty-two patients completed 36 months and 20 patients 42 months of treatment. Results:The BMD increased for up to 30-36 months and plateaued thereafter. In the whole study group, the maximum increase of BMD was 5.0% in the lumbar spine (P < 0.001), 5.9% (P < 0.01) in the femoral neck, 4.9% (NS, P > 0.05) in the Ward's triangle and 8.2% (P < 0.001) in the trochanter area. The serum concentrations of PICP (202.6 Ϯ 11.5 vs 116.3 Ϯ 5.4 mg/l; mean -Ϯ S.E.M.) and ICTP (10.5 Ϯ 0.6 vs 4.4 Ϯ 0.3 mg/l) doubled (P < 0.001) during the first 6 months of GH treatment but returned to baseline by the end of the study (130.0 Ϯ 10.4 and 5.6 Ϯ 0.7 mg/l respectively), despite constantly elevated serum IGF-I levels (39.6 Ϯ 4.1 nmol/l at 42 months vs 11.9 Ϯ 0.9 nmol/l at baseline; P < 0.001). The responses to GH treatment of serum IGF-I, PICP, ICTP (P < 0.001 for all; ANOVA) and of the BMD in the lumbar spine (P < 0.05), in the femoral neck and the trochanter (P < 0.001 for both) were more marked in men than in women. At the end of the study the BMD had increased at the four measurement sites by 5.7-10.6% (P < 0.01-0.001) in patients with at least osteopenia at baseline and by 0.1-5.3% (NS P < 0.05) in those with normal bone status (P < 0.001 for differences between groups; ANOVA). Among patients who completed 36-42 months of treatment, the number of those with at least osteopenia was reduced to more than a half. The response of BMD to GH treatment was more marked in young than in old patients at three measurement sites (P < 0.05-<0.001; ANOVA). In the multiple regression analysis the gender and the pretreatment bone mass appeared to be independent predictors of three measurement sites, whereas the age independently determined only the vertebral BMD. Conclusions: GH treatment in GH-deficient adults increased BMD for up to 30-36 months, with a plateau thereafter. Concurrently with the plateau in BMD the bone turnover rate normalized. From the skeletal point of view GH-deficient patients exhibiting osteopenia or osteoporosis should be considered as candidates for GH supplementation of at least 3-4 years.

Objective: To study whether levothyroxine (LT 4 ) suppressive therapy exposes patients with differentiated thyroid cancer (TC) to an increased risk of osteoporosis. Design and Methods: Markers of bone formation (serum alkaline phosphatase (ALP), osteocalcin (OC), type I procollagen carboxyterminal (PICP) and aminoterminal (PINP) propeptide) and resorption (serum type I collagen carboxyterminal telopeptide (ICTP) and urine hydroxyproline (HOP)), as well as serum intact parathyroid hormone (PTH), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25(OH) 2 -D) were measured in 29 patients (25 women, 4 men) with a median age of 45 years, and in 38 age-and sexmatched controls. In a subgroup of 14 patients the measurements were repeated after 5 weeks' interruption of LT 4 therapy. Since the primary treatment of TC the patients had used TSH suppressive doses of LT 4 (a mean daily dose of 215 mg) for 9 to 11 years. The bone mineral density (BMD) of patients and controls was measured by dual energy X-ray absorptiometry. Results: When on T 4 therapy, patients had significantly higher mean levels of ALP (þ21%, P < 0.05), OC (þ35%, P < 0.01), PICP (þ10%, P < 0.05), PINP (þ46%, P < 0.001), ICTP (þ21%, P < 0.05), and HOP (þ37%, P < 0.001) compared with controls. After stopping treatment, OC (¹42%, P < 0.001), PINP (¹7%, P < 0.05), and ICTP (¹54%,P < 0.001) decreased, whereas PICP (þ24%, P < 0.001) and 1,25-(OH) 2 D (þ29%, P < 0.01) increased. BMD of the lumbar spine and the upper femur was similar in patients and controls. Conclusions: Patients with differentiated TC have high bone turnover when on LT 4 suppressive therapy. After withdrawing treatment both bone formation and resorption decrease acutely. During development of hypothyroidism, serum PICP and PINP, which form from the same type I procollagen molecule and should change similarly, behaved differently. This may be due to different effects of hypothyroidism on their removal through separate receptors in the liver.

Summary:Osteoporotic fractures are potential long-term complications of bone marrow transplantation (BMT). We previously reported that bone mineral density (BMD) of patients undergoing allogeneic BMT decreased by 6% to 9% during the first 6 months after BMT and that bone turnover rate was still increased 1 year after BMT. BMT patients do not need lifelong immunosuppressive treatment, which should offer favorable circumstances for the recovery of BMD. Thus, 27 (14 women, 13 men) of 29 long-term survivors of our previous study were invited to a follow-up study at a median of 75 months after BMT. From 12 months after BMT the BMD of the lumbar spine had increased by 2.4% (P ‫؍‬ 0.002). The respective changes in femoral sites were ؉4.1% in the femoral neck (P ‫؍‬ 0.087), 4.0% in the trochanter (P ‫؍‬ 0.095), ؉4.7% in Ward's triangle (P ‫؍‬ 0.072) and ؉1.4% in the total hip (P ‫؍‬ 0.23). The markers of bone formation, serum osteocalcin and type I procollagen aminoterminal propeptide (PINP) had returned to control levels, but out of the markers of bone resorption the mean level of serum type I carboxyterminal telopeptide (ICTP) was 41% higher (P ‫؍‬ 0.0001) and that of urinary type I collagen N-terminal telopeptide/creatinine (NTx) 41% lower (P ‫؍‬ 0.0002) in patients than in con Keywords: bone marrow transplantation; osteoporosis; bone mineral density; bone markers; vitamin D Osteoporosis and osteoporotic fractures are potential longterm complications of not only solid organ transplants 1 but also of the bone marrow. 2,3 In our prospective study of 44 patients undergoing allogeneic bone marrow transplantation (BMT) bone mineral density (BMD) decreased by 6% in the lumbar spine and by 7% to 9% in the three femoral sites during the first 6 post-transplant months; no significant further decline occurred between 6 and 12 months. 2 Shortly after BMT bone loss was explained by uncoupling between increased bone resorption and decreased bone formation. 2 At the end of 1-year follow-up both resorption and formation markers were elevated, indicating accelerated bone turnover in survivors. 2 Unlike transplant recipients of solid organs, recipients of hemopoietic transplants do not need lifelong immunosuppression, and glucocorticoids and cyclosporine A can usually be stopped. This fact, together with a relatively young age of BMT recipients offer the bone favourable circumstances to recover, the magnitude of which has not been addressed in previous studies. Thus, we invited the long-term survivors of our original patient population to a follow-up study, in which their BMD and bone turnover state were re-evaluated at a median of 6 years after BMT. The values were compared to those obtained at the end of the previous 1-year follow-up, and biochemical data were compared to those produced by sex-matched controls. The vitamin D status of the patients was also evaluated. Patients and methods PatientsTwenty-nine of 44 patients who had received an allogeneic bone marrow transplant and taken part in our previous study were still alive and...