Summary:Transplantation of solid organs including heart, kidney, and liver is associated with rapid bone loss and increased rate of fracture; data on bone marrow transplantation recipients (BMT) are scarce. The purpose of the present study was to examine the magnitude, timing, and mechanism of bone loss following allogeneic BMT, and to study whether bone loss can be prevented by calcium with or without calcitonin. Sixty-nine patients undergoing allogeneic 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. They were randomized to receive either no additional treatment (n ‫؍‬ 22), or oral calcium 1 g twice daily for 12 months (n ‫؍‬ 12) or the same dose of calcium 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 spine 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) and aminoterminal propeptide (PINP), serum type I collagen carboxyterminal telopeptide (ICTP)). Serum testosterone was assayed in men. Calcium with or without calcitonin had no effect on bone loss or bone markers; consequently the three study groups were combined. During the first 6 post-transplant months BMD decreased by 5.7% in the lumbar spine and by 6.9% to 8.7% in the three femoral sites (P Ͻ 0.0001 for all); no significant further decline occured between 6 and 12 months. Four out of 25 assessable patients experienced vertebral compression fractures. Markers of bone formation reduced: B-ALP by 20% at 3 weeks (P ‫؍‬ 0.027), PICP by 40% (P Ͻ 0.0001) and PINP by 63% at 6 weeks (P Ͻ 0.0001), with a return to baseline by 6 months. The marker of bone resorption, serum ICTP was above normal throughout the whole observation period, with a peak at 6 weeks (77% above baseline, P Ͻ 0.0001). In male patients serum testosterone decreased reaching a nadir (57% below baseline) at 6 weeks (P ‫؍‬ 0.0003). In conclusion, significant bone loss occurs after BMT. It results from imbalance between reduced bone formation and increased bone resorption; hypogonadism may be a contributing factor in men. Bone loss can not be prevented by calcium with or without calcitonin.

Short-term alcohol administration causes transitory hypoparathyroidism. This decline in the secretion of parathyroid hormone accounts at least in part for the transient hypocalcemia, hypercalciuria, and hypermagnesuria that follow alcohol ingestion.

In patients on antiepileptic drugs, bone loss has been mainly demonstrated at radial sites using old technology and has been ascribed to drug-induced vitamin D deficiency rather than to any direct effects of the treatment on bone cells. We examined 38 epileptic patients (24 women and 14 men) aged 20-49 years who were using either carbamazepine or phenytoin or both. Bone mineral density (BMD) at the lumbar spine and three femoral sites was measured by dual-energy x-ray absorptiometry (DXA) and serum and urine markers of bone and mineral metabolism were determined. The latter included the C-terminal extension peptide of type I procollagen (PICP), a putative serum marker of bone formation, and the cross-linked carboxyl-terminal telopeptide of human type I collagen (ICTP), a novel serum marker of bone matrix degradation. In female patients on phenytoin, weight- and height-adjusted BMD was reduced at the femoral neck and the Ward's triangle (p < 0.05) but was at the control level in the other patient groups at all four measurement sites. Compared with controls, the serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were reduced by 26% (p < 0.01) and by 27% (p < 0.001) in female patients. These changes were independent of the therapy used. They were not present in male patients. For both genders the serum levels of vitamin D binding protein were normal. Both female and male patients had hypocalcemia, but women only showed hypocalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Acute alcohol intoxication causes diuresis presumably resulting from inhibition of vasopressin (also called antidiuretic hormone) release from the posterior pituitary gland. In contrast, in alcoholics during withdrawal from alcohol, vasopressin release is stimulated, resulting in water retention (antidiuresis) and dilutional hyponatremia. The purpose of this study was to evaluate the role of this biphasic response of vasopressin secretion to alcohol in normal persons. We studied eight healthy men who took part in two study sessions: one involving the ingestion of ethanol (1.2 g/kg of body weight) and the other the ingestion of the same volume of fruit juice during 3 hr from 6 to 9 PM. Starting at 6 AM the following morning, subjects were loaded with water (20 ml/kg of body weight within 15 min). During the first 3 hr of the study, ethanol intake increased diuresis, whereas from midnight to 6 AM, a phase of antidiuresis was obtained. Antidiuresis continued during water loading when the retention of water was 44 +/- 6% during the alcohol experiment and 12 +/- 4% during the control session (p < 0.05). During the alcohol-induced diuresis, the plasma arginine vasopressin levels did not differ from the control experiment, but were higher during the phase of antidiuresis from 10 PM to 6 AM (p < 0.05- < 0.01). Also, after water loading at 8 and 9 AM, they were higher in the alcohol study than in the control experiment (p < 0.05). After alcohol ingestion, serum osmolality was higher than the corresponding control values from 8 PM to 2 AM (p < 0.01- < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)