Combining Bone-Building Drugs Key to Making Bones Stronger

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Two drugs used to treat osteoporosis may be better than either alone in maintaining bone density.

Dr. Benjamin Leder and his colleagues at Massachusetts General Hospital found that combining teriparatide (Forteo) and denosumab (Prolia) improved bone density tests among a group of post menopausal women with osteoporosis after a year better than any benefits that currently available drugs provide on their own.

Maintaining bone strength is about managing the creation and destruction of bone; teriparatide works by both stimulating bone formation and preventing bone decay, while denosumab primarily inhibits bone loss, so the dual actions may have contributed to the combination’s success.

Prior studies that combined the popular bisphosphonates, which include Fosamax, with teriparatide have been unsuccessful, but the researchers, who reported their findings in the journal Lancet, believe that denosumab may work better with teriparatide because it can block teriparatide’s bone decaying activity more effectively. Bisphosphonates, like denosumab, also blocks the destruction of bone but through a different pathway.

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Osteoporosis is more common among women following menopause, since the cells that break down or cause resorption of bone, called osteoclasts, and the cells that form new bone, called osteoblasts, become more active. However, over time, the osteoclasts tend to overtake the bone-building processes, which leads to lower bone density and a higher risk for fractures.

In the study, the researchers separated the 94 female study participants into three groups. One received the combined teriparatide  and denosumab therapy while the other two groups took one or the other medication alone.

The participants’ had their bone density measured and blood tests conducted at three months, six months and at the end of the year-long study. Those with the combined drug therapy showed a 9.1% increase in bone density of the lumbar spine compared to a 6.2% increase among the teriparatide only group, and a 5.5% increase among the denosumab only group. They also showed similar increases in bone density of the hip.

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“Unlike the combination between bisphosphonate and teriparatide, denosumab is fully able to inhibit the amount of bone resorption that teriparatide usually induces, while still allowing for some bone formation to occur, and it’s that difference that I think accounts for the increase in bone density that you see with these two drugs as opposed to other combinations,” says study author Dr. Benjamin Leder, an endocrinologist at Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School.

The study involved a small number of patients, and did not follow the participants long enough to see if the higher bone density contributed to fewer falls or fractures. But the researchers are planning more studies to investigate those questions, and if the results hold, the combination could provide a new way of helping women who are past menopause to maintain their bone strength.