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Pamidronate Reduces Bone Loss after Allogeneic Stem Cell Transplantation

Royal Melbourne Hospital (A.P.G., P.S., J.S., P.R.E.), Parkville, Victoria 3050, Australia; Peter MacCallum Cancer Centre (J.R.), East Melbourne, Victoria 3002, Australia; Alfred Hospital (A.P.S.), Prahran, Victoria 3181, Australia; Westmead Hospital (K.B.), Westmead, New South Wales 2145, Australia; Royal Adelaide Hospital (C.H.), Adelaide 5000, Australia; and Royal Perth Hospital (R.H.), Perth, Western Australia 6000, on behalf of the Australasian Bone Marrow Transplant Cooperative Study Group

Address all correspondence and requests for reprints to: Professor Peter R. Ebeling, Department of Medicine, University of Melbourne, Western Hospital, Footscray 3011, Australia. E-mail: peterre{at}unimelb.edu.au.

Background: Rapid bone loss occurs from the proximal femur after allogeneic stem cell transplantation (alloSCT).

Objective: The objective of the study was to evaluate effects of high-dose pamidronate therapy on bone loss (BMD) after alloSCT.

Design: This was a randomized, multicenter, open-label, 12-month prospective study of iv pamidronate (90 mg/month) beginning before conditioning vs. no pamidronate. All 116 patients also received calcitriol (0.25 µg/d) and calcium (1000 mg/d), which were continued for another year.

Main Outcome Measures: Primary objectives were to compare changes in BMD 12 months after alloSCT at the femoral neck, lumbar spine, and total hip between the treatment arms and assess influences of glucocorticoid and cyclosporin therapy on these changes.

Results: Pamidronate reduced bone loss at the spine, femoral neck, and total hip by 5.6, 7.7, and 4.9% (all P 0.003), respectively, at 12 months. However, BMD of the femoral neck and total hip was still 2.8 and 3.5% lower than baseline, respectively (P < 0.05) with pamidronate. Only differences at the total hip remained significant between the two groups at 24 months. Benefits were restricted to patients receiving an average daily prednisolone dose greater than 10 mg and cyclosporin therapy for more than 5 months within the first 6 months of alloSCT.

Conclusions: Pamidronate markedly reduced but did not completely prevent postallogeneic bone marrow transplantation bone loss. BMD benefits were greatest in patients on higher doses of immunosuppressive therapy, but most were lost 12 months after stopping pamidronate. Studies of more potent bisphosphonates or anabolic therapy with PTH after alloSCT are warranted with the aim of durable maintenance of bone mass.

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