Zoledronic acid prevents bone loss after liver transplantation: a randomized, double-blind, placebo-controlled trial.
BACKGROUND
Clinically important rapid bone loss occurs within 3 to 6 months after liver transplantation and may be associated with osteoporotic fractures.


OBJECTIVE
To determine whether bisphosphonate treatment with zoledronic acid reduces transplant-related bone loss more than placebo in adults having liver transplantation for chronic liver disease.


METHODS
12-month randomized, double-blind, placebo-controlled trial.


METHODS
2 large liver transplantation centers in Australia.


METHODS
62 adults having liver transplantation for chronic liver disease.


METHODS
Infusions of zoledronic acid, 4 mg (n = 32), or saline (n = 30) were given within 7 days of transplantation and again at months 1, 3, 6, and 9 after transplantation. All patients received supplementation with calcium carbonate, 600 mg/d, and ergocalciferol, 1000 U/d.


METHODS
The primary outcome was bone mineral density (BMD) measured by dual x-ray absorptiometry before transplantation and 3, 6, and 12 months later. Secondary outcomes included bone turnover markers that were measured before transplantation and 1, 3, 6, 9, and 12 months later.


RESULTS
There were statistically significant interactions between treatment effects and time for BMD measurements at the lumbar spine (P = 0.002), femoral neck (P = 0.001), and total hip (P < 0.001). Differences in acute bone loss 3 months after transplantation favored zoledronic acid over placebo. Differences between groups in percentage change from baseline adjusted for baseline weight and serum parathyroid hormone (PTH) level were 4.0% (95% CI, 1.1% to 7.0%) for the lumbar spine, 4.7% (CI, 1.9% to 7.6%) for the femoral neck, and 3.8% (CI, 1.7% to 6.0%) for the total hip. At 12 months after transplantation, the difference in percentage change from baseline between the 2 groups adjusted for baseline weight and serum PTH level was 1.1% (CI, -2.1% to 4.4%) for the lumbar spine, 2.7% (CI, 0.0% to 5.4%) for the femoral neck, and 2.4% (CI, 0.1% to 4.7%) for the total hip. Treatment with zoledronic acid induced temporary secondary hyperparathyroidism and postinfusion hypocalcemia statistically significantly more often than did placebo.


CONCLUSIONS
The trial was not powered to assess fractures, and 10 of 62 (16%) patients were not included in adjusted analyses because of missing weight or serum PTH measurements.


CONCLUSIONS
Treatment with zoledronic acid can prevent bone loss within the first year after liver transplantation.
Crawford
Bronwyn A L
BA
Royal Prince Alfred Hospital, University of New South Wales, NHMRC Clinical Trials Centre, and University of Sydney, New South Wales, Australia.
Kam
Cherie
C
Pavlovic
Julie
J
Byth
Karen
K
Handelsman
David J
DJ
Angus
Peter W
PW
McCaughan
Geoffrey W
GW
D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D006887:Hydroxycholecalciferols / Q000097:blood; D006962:Hyperparathyroidism, Secondary / Q000139:chemically induced; D006996:Hypocalcemia / Q000139:chemically induced; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D017093:Liver Failure / Q000150:complications / Q000601:surgery; D016031:Liver Transplantation / Q000009:adverse effects*; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D010281:Parathyroid Hormone / Q000097:blood; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D006887:Hydroxycholecalciferols; D007093:Imidazoles; D010281:Parathyroid Hormone; D000077211:Zoledronic Acid