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Long-term use of bone-building osteoporosis drugs
Bisphosphonates are designed to slow or stop the bone loss that occurs during the body's bone remodeling cycle, or the natural process that involves removal and replacement of bone tissue.
Two separate studies by scientists from Hospital for Special Surgery (HSS) and Columbia University Medical Center revealed data suggesting that long-term suppression of bone remodeling by bisphosphonate therapys may alter the material properties of bone, potentially affecting the bone's mechanical integrity and potentially contributing to the risk of atypical fractures.
"Eventhough bisphosphonates have demonstrated an improvement in bone quantity, little if anything is known about the effects of these drugs on bone quality," said Brian Gladnick, BS, representing a team of researchers at HSS in New York.
Scientists at Columbia reviewed the bone structure of 111 postmenopausal women with primary osteoporosis, 61 of whom had been taking bisphosphonates for a minimum of four years and 50 controls taking calcium and vitamin D supplements.
This study observed that bisphosphonate use improved structural integrity early in the course of therapy, but those gains were diminished with long-term therapy.
"In the early therapy period, patients using bisphosphonates experienced improvements in all parameters, including decreased buckling ratio and increased cross-sectional area," said Melvin Rosenwasser, MD, orthopaedic surgeon for Columbia University Medical Center. "However, after four years of use, these trends reversed, revealing an association between prolonged treatment and declining cortical bone structural integrity".
Researchers at both institutions noted that the culprit behind the diminishing results appears to be the fact that bisphosphonates suppress the body's natural process of remodeling bone. "Recent research suggests that suppressed bone remodeling from long-term bisphosphonate use might result in brittle bone that is prone to atypical fractures," said Gladnick.
The researchers added that more studies are needed to determine the true efficacy of the long-term clinical use of bisphosphonates for the therapy of osteoporosis, and that the results of their studies will not likely affect clinical practice in the near future.
"Bisphosphonate use still is a very effective solution that prevents bone loss in most patients and no one is recommending that physicians avoid prescribing these," said Dr. Rosenwasser. "However, as baby boomers age and continue to remain active, it is important that we conduct more research and develop sustainable, safe and effective therapys for osteoporosis."
In a second unrelated prospective pilot study, conducted at HSS and funded in part by the NIH, scientists reviewed the bone composition of 21 post-menopausal women who were treated for femoral fractures. Of these, 12 patients had a history of bisphosphonate therapy for an average of 8.5 years, while nine had not had bisphosphonate therapy.
Samples of bone were removed from each patient's femur during surgical placement of a femoral nail. Both micro-architecture and material properties of the bone were analyzed.
The study observed that, eventhough there were no differences in bone micro-architecture between groups, the material properties of bone in bisphosphonate-treated patients displayed reduced bone tissue heterogeneity, which appears to be linked to reduced strength and potentially may contribute to the presentation of atypical fractures.
"Patients who had been treated with bisphosphonates showed a reduction in tissue heterogeneity, specifically with mineral content and crystal size compared with the control group," Gladnick said. "This tells us that there appears to be some measurable differences in bone quality parameters in patients on long-term bisphosphonate treatment, which might contribute to the development of atypical fractures".
Posted by: Emily Source