Prevention of bone loss after heart transplantation with antiresorptive therapy: a pilot study.
BACKGROUND
Heart transplantation, with its attendant glucocorticoid and cyclosporine therapy, has deleterious effects on the skeleton. We have previously reported rapid bone loss and high fracture rates (36% of patients) during the first year after heart transplantation. The bone loss was accompanied by declines in serum 1,25-dihydroxyvitamin D and osteocalcin levels and increased urinary excretion of markers of bone resorption (hydroxyproline, pyridinoline, and deoxypyridinoline). We therefore investigated whether bone loss could be prevented by bisphosphonates, agents that inhibit bone resorption.


METHODS
Serial measurements of bone mineral density (BMD) and biochemical indexes of mineral metabolism were compared in 18 group A patients who received a single intravenous infusion of pamidronate (60 mg) within 2 weeks of heart transplantation, followed by 4 cycles of oral etidronate (400 mg daily for 14 days every 3 months) and oral calcitriol 0.25 microg daily, to those of 52 patients who previously underwent transplantation (group B) who did not receive antiresorptive therapy. Both groups received elemental calcium 1000 mg and vitamin D 400 IU daily.


RESULTS
At 12 months after transplantation, there was virtually no lumbar spine bone loss in group A patients, whereas lumbar spine BMD had declined significantly in group B patients (0.2% +/- 0.9% vs 6.8% +/- 1.0%, respectively; P < .0001). Similarly, femoral neck BMD fell by 10.6% +/- 1.1% in group B patients and by only 2.7% +/- 1.4% in group A patients (P < .0001). Three incident vertebral fractures occurred in two group A patients, whereas 17 group B patients sustained 30 incident vertebral fractures, one hip fracture and three episodes of rib fractures (P < .02; test of proportions). With respect to markers of bone resorption, urinary deoxypyridinoline fell by 51% +/- 9% in group A patients and increased by 65% +/- 22% in group B patients by 3 months after transplantation (P < .0001).


CONCLUSIONS
In summary, heart transplant recipients treated with bisphosphonates and replacement doses of calcitriol sustained less bone loss and fewer fractures than those treated with calcium and vitamin D. We conclude that bisphosphonate therapy, in conjunction with calcitriol, shows promise for prevention of transplantation-related osteoporosis.
Shane
E
E
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. es54@columbia.edu
Rodino
M A
MA
McMahon
D J
DJ
Addesso
V
V
Staron
R B
RB
Seibel
M J
MJ
Mancini
D
D
Michler
R E
RE
Lo
S H
SH
D015502:Absorptiometry, Photon; D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control; D002117:Calcitriol / Q000008:administration & dosage; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D012968:Etidronic Acid / Q000008:administration & dosage; D005260:Female; D050723:Fractures, Bone / Q000209:etiology; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D000077268:Pamidronate; D010281:Parathyroid Hormone / Q000097:blood; D010865:Pilot Projects; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
D000596:Amino Acids; D015415:Biomarkers; D004164:Diphosphonates; D007166:Immunosuppressive Agents; D010281:Parathyroid Hormone; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; C036020:deoxypyridinoline; D003404:Creatinine; D002117:Calcitriol; D012968:Etidronic Acid; D000077268:Pamidronate; D002118:Calcium