Prevention of osteoporosis after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol.
BACKGROUND
Accelerated bone loss is a well-recognized complication after cardiac transplantation (HTx) due to immunosuppressive therapy. The purpose of this prospective, longitudinal, randomized, placebo-controlled, double-blind study was to investigate the effect of calcitriol (1,25-dihydroxyvitamin D3) in the prevention of bone loss and fracture rate after HTx.


METHODS
Basic therapy included 1000 mg of calcium daily and sex hormone replacement in hypogonadal patients. A total of 132 patients (111 male, 21 female; mean age: 51+/-10 years; 35+/-25 months after HTx) were randomized to 0.25 microg of calcitriol or placebo. Bone mineral density (BMD, g/cm2; T score, %) of the lumbar spine and x-rays for the assessment of vertebral fractures were performed at baseline and after 12, 24, and 36 months. Biochemical indexes of mineral metabolism were measured every 3 months.


RESULTS
Overall BMD was significantly decreased after HTx (T score 87+/-13%). BMD increased continuously within the study period in the calcitriol group (1 year: 2.2+/-4.8%; 2 years: 3.9+/-5.4%; 3 years: 5.7+/-4.4%) as well as in the placebo group (1 year: 1.8+/-4.9%; 2 years: 3.7+/-6.5%; 3 years: 6.1+/-7.8%) without statistical difference between the groups. Fracture incidence was low during the study interval (1 year: 2.0%; 2 years: 3.4%; 3 years: 0%). Hypogonadism (20%) was associated with a lower BMD (78+/-12% vs. 88+/-12%; P<0.01) and a higher increase (35%) after hormone replacement in comparison to normogonadal patients. Increased intact parathyroid hormone and bone resorption markers decreased significantly during therapy.


CONCLUSIONS
Calcium supplementation and sex hormone replacement in hypogonadism proved a sufficient long-term prevention therapy to improve decreased BMD and to prevent fractures after HTx. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role in the long-term bone loss and should therefore be monitored and treated adequately. Low-dose calcitriol demonstrated no significant extra benefit regarding BMD and fracture rate in the long-term period after HTx.
Stempfle
H U
HU
Medizinische Klinik, Klinikum Innenstadt, Department of Cardiology, Ludwig-Maximilians University, Munich, Germany.
Werner
C
C
Echtler
S
S
Wehr
U
U
Rambeck
W A
WA
Siebert
U
U
Uberfuhr
P
P
Angermann
C E
CE
Theisen
K
K
Gärtner
R
R
D000328:Adult; D015519:Bone Density / Q000187:drug effects; D002117:Calcitriol / Q000008:administration & dosage; D002136:Calcium, Dietary / Q000008:administration & dosage; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D013739:Testosterone / Q000008:administration & dosage
D002136:Calcium, Dietary; D004967:Estrogens; D007166:Immunosuppressive Agents; D013739:Testosterone; D002117:Calcitriol