Unfortunately for many with the bone-thinning disease osteoporosis, combining two currently available types of osteoporosis drugs does not improve bone density, according to a Massachusetts General Hospital (MGH) study in the September 25 issue of the New England Journal of Medicine. Men with osteoporosis who received both alendronate and parathyroid hormone (PTH) actually developed a lower bone density at the end of the almost three-year study than did men receiving PTH by itself.

Osteoporosis is a well-recognized complication of ankylosing spondylitis (AS) and related spondyloarthropathies, and can occur even in the early stages of disease.

Study Breakdown
Previously, the Food and Drug Administration (FDA) approved alendronate (a bisphosphonate) and PTH injections to treat osteoporosis in men and women. These drugs work in complementary fashion to increase bone density so these researchers wanted to study whether combining both medications produced better results.

Researchers thought that the combination group would do the best and were surprised by the outcome. Study leader Joel Finkelstein, MD, MGH endocrinologist, points out that while it seemed likely that combining these two medications would increase bone density in patients more than giving either one of the medications alone, “animal studies investigating combination therapy gave conflicting results.”

The MGH researchers started two studies involving a combination of these drugs – one in men with osteoporosis (as mentioned in this article) and one in postmenopausal women (not yet complete but producing similar preliminary results as the men’s study).

In this study, 83 men were randomly assigned to three groups. The first received daily PTH injections; the second was treated with alendronate; the third received both medications. Researchers studied four key bone density measurements (lower spine, hip bone, forearm bone, and the total body) five times during the 30-month study. Spine bone density was also measured by computerized tomography.

Results
Combination therapy improved bone density in the spine more than alendronate alone, yet neither improved spine bone density as much as PTH alone. The same was true for the hip bone area. At the forearm, alendronate or combination therapy led to a slight increase in bone density; PTH alone produced a slight decrease. Regarding total body bone density, there were no significant differences among the three groups.

What This Means
Researchers believe that alendronate suppresses bone resporption, interfering with a process required for bone regrowth. This may reduce the effectiveness of combination therapy. “Bone resporption could release growth factors that stimulate bone formation and are necessary to get the full effect of PTH,” explains Finkelstein. “At this time, we are generally recommending that anyone taking PTH use it by itself and that anti-resorptive therapies be stopped before starting PTH therapy.”

Further research is needed to determine the best bone-density-resorting strategies for patients and to improve understanding of the long-term effects of PTH treatment, according to the study’s authors. Additional studies are needed to determine if PTH therapy reduces fractures more when given alone or when given in combination with an anti-resporptive drug.