BOSTON, Mass. –  Alendronate reduces the ability of once-daily teriparatide to stimulate new bone formation in osteoporotic men, according to new research by Joel A. Finkelstein, MD, of Massachusetts General Hospital in Boston. The findings, which appear in the May issue of the Journal of Clinical Endocrinology and Metabolism,1 are consistent with previous research suggesting that alendronate impairs teriparatide's ability to increase bone mineral density (BMD) of the lumbar spine and femoral neck in men.2 Similar results have been seen among postmenopausal women with osteoporosis.3

"These findings suggest that bone resorption plays a role in the ability of teriparatide to increase bone formation," the researchers conclude. Alendronate may attenuate the anabolic action of teriparatide by exerting its effect on bone either indirectly via a mechanism that requires it to increase osteoclastic bone resorption or via a direct stimulatory effect on osteoblastic bone formation, they speculate.

The nonblinded, randomized, controlled trial of 63 men aged 46–85 with low spine and/or hip BMD sought to determine whether teriparatide increases osteoblast activity when its ability to increase osteoclast activity is suppressed by alendronate. Study participants received either 10 mg alendronate daily (Group 1), 37 µg subcutaneous teriparatide daily (Group 2) or both (Group 3) for 30 months. Teriparatide therapy was initiated at 6 months. The dose used is higher than that currently approved in the US, but similar to doses used in other clinical trials. The primary endpoint was the change in serum N-telopeptide (NTX), osteocalcin (OC), and amino-terminal propeptide of type 1 procollagen (P1NP).

In men receiving teriparatide monotherapy, levels of all bone turnover markers increased markedly in the first 6 months of teriparatide administration and then declined toward baseline in the next 18 months. In men who received combination therapy, however, bone turnover marker levels declined in the first 6 months (while receiving alendronate alone) and then returned to baseline levels of serum NTX or above in terms of OC and amino-terminal propeptide of P1NP after teriparatide was added. Changes in each marker were significantly different between Groups 1 and 2 (all P values <.001), Groups 1 and 3 (all P values <.001), and Groups 2 and 3 (all P values <.03), the study showed.

New findings confirm earlier reports

Stephen Honig, MD, director of the osteoporosis center at New York University Hospital for Joint Diseases in New York City, told CIAOMed that "there have been ample studies that have shown the most effective way of using these drugs in terms of BMD improvements is sequentially, starting with teriparatide followed by bisphosphonates, which are osteoclast inhibitors and delay the effectiveness of teriparatide."

Dr. Honig pointed out that initially it was thought that bisphosphonates combined with a drug that stimulates osteoclasts would produce added benefits. However, "you don't get the same gains when you use both agents at the same time," he told CIAOMed.

Robert Recker, MD, professor of medicine and chief of the section of endocrinology and director of the Osteoporosis Research Center at Creighton University at Omaha, Nebraska, said that "an intuitive evaluation of the new findings is that if you give a bisphosphonate like alendronate, you may not get as much out of teriparatide as if you had not. The new study does not address how the combination affects fracture risk."

"If you prescribe teriparatide after a male patient [has] been on a bisphosphonate, the benefit of the teriparatide [is] blunted," Dr. Recker said. "If you think a patient should get teriparatide, the best thing is to start with it," he said, adding that, due to a black box warning, teriparatide cannot be given for longer than 24 months anyway.

References

  1. Finkelstein JS, Leder BZ, Burnett SA, et al. Effects of teriparatide, alendronate, or both on bone turnover in osteoporotic men. J Clin Endocrinol Metab. 9 May 2006; [Epub ahead of print]
  2. Finkelstein JS, Hayes A, Hunzelman JL, et al. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med. 2003;349:1216-1226.
  3. Black DM, Greenspan SL, Ensrud KE, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med. 2003;349:1207-1215.