Oral bisphosphonates were another story. Potential safety issues with them include osteonecrosis of the jaw (ONJ), atypical fractures, and esophageal cancer. However, Dr. Saag did not think that was "that big a concern."
"We know from the oncology literature that it’s maybe [1%-10% of patients who] get these monthly infusions of the potent IV bisphosphonates" who may go on to develop ONJ, he said. But in the setting of osteoporosis, the rough incidence is more likely to be between 1 per 10,000 and 1 per 100,000, he said.
"Calcium and vitamin D used to be the least controversial part of any lecture on osteoporosis."
Atypical femoral fractures have been associated with bisphosphonates, but Dr. Saag said that the past evidence has been circumstantial. However, a recent observational study from Scandinavia found a significant association between bisphosphonate use and the risk of subtrochanteric and femoral shaft fractures in older women (JAMA 2011;305:783-9).
Moving on to denosumab, Dr. Saag praised the drug as highly potent antiresorptive with a well-defined mechanism of action. However, he cited evidence of serious infectious adverse events in four randomized, controlled trials: DEFEND (J. Clin. Endocrinol. Metab. 2008;93:2149-57), DECIDE (J. Bone Miner. Res. 2009;24:153-61), STAND (ASBMR 2008, poster M395), and FREEDOM (N. Engl. J. Med. 2009;361:756-65).
"There appears to be a signal of cellulitis," he said.
A study of the combination of zoledronate and teriparatide and their effect on lumbar spine BMD yielded an interesting point about sequencing (J. Bone Miner. Res. 2011;26:503-11).
"When you give bisphosphonate in a pulsatile way, in contrast to a continuous exposure with the weekly therapy, it actually seems to have less suppressive effects on osteoblasts. And that may be why we see [that] the combination of the two results in more increase in bone mineral density than [does] either agent alone," said Dr. Saag. "We don’t know whether that equates to fracture risk reduction."
Support for this meeting came from Abbott, Amgen, Centocor, Genentech, Human Genome Science, and UCB. Dr. Saag disclosed research funding from the National Institutes of Health, the Agency for Healthcare Research and Quality, the American College of Rheumatology (ACR), Amgen, Lilly, and Merck. He is a member of the board of trustees of the National Osteoporosis Foundation and is chair of the quality of care committee of the ACR; he serves on advisory boards at Amgen, Lilly, Merck, and Novartis.