While fracture reduction has been the gold standard by which the value of anti-osteoporotic medications are judged, physicians have also looked to increased in BMD as a potential guideline for shorter term results. But a recent study reported at the ACR confirms earlier insights that the benefits of antiresorptive therapy on fracture risk may be significant even when improvement in BMD is insignificant.
Based on recent work demonstrating that less than 20% of the observed fracture reduction from anti-resorptive treatment is explained by BMD increases, Lindsay et al reanalyzed data from the HIP and VERT and HIP phase III clinical studies. In these trials, nearly 9,000 patients were randomized to either risedronate 5 mg daily or placebo, in addition to 1,000 mg calcium daily, plus vitamin D if their baseline levels were low.
The relationships between new vertebral fractures and changes in lumbar spine BMD were examined over 3 years. The researchers found that "larger increases in BMD do not translate into larger decreases in fracture incidence in patients on active therapy." Indeed, even "a modest positive change in BMD" due to anti-resorptive therapy seemed "indicative of a therapeutic benefit on fracture risk." They concluded that "BMD differences between established therapies cannot be interpreted as differences in fracture efficacy." Further, because the authors found that even moderate increases in BMD offer treatment benefit that is not significantly different from larger increases, they suggested that there may be a threshold above which further increases in BMD have little effect on fracture benefit.
The investigators suggested that their findings emphasize the need for further research to determine how osteoporosis therapies influence other elements of bone quality that affect the risk of fracture, such as bone turnover and bone micro-architecture. Indeed, the general thinking is that bisphosphonates reduce bone resorption and thus bone turnover, thereby reducing fracture risk. Medications such as corticosteroids increase the rate of bone resorption and thus bone turnover. Perhaps when bone turnover is increased, bone is weaker, which may be one concern to be addressed in fracture research.
In the meantime, this research is more evidence to support the physician who tells the patient that the lack of a significant change in BMD does not mean that anti-resorptive therapy is not working. As long as the BMD does not fall, therapy need not be changed, the authors advised.
 Lindsay R, Adachi JD, Barton IP, Manhart MD. Fracture Risk Reduction Due to Antiresorptive Treatment is Independent of the Magnitude of BMD Improvement. Arthritis Rheum. 2003 Sep;48(9):S84. (Abstract #101is available on the website of the ACR. Search for abstract 101.)
 Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med. 2002 Mar;112(4):281-9.