Can I take prescription osteoporosis medications in combination with each other? Which medications could I use together to get more improvement in my bones?

In the case of treating osteoporosis, a combination of agents can mean more BMD than is gained by using one agent alone. Because there are no data yet on the risk of fractures, it's not clear if increasing BMD using combination therapies necessarily decreases fracture risk more, which is the goal of combining therapies. Treatment with two drugs is clearly more expensive than treating with one drug alone, and the risk for developing side effects increases. According to the 2004 Surgeon General's Report on Bone Health, combination therapies should be reserved for individuals whose bone mass is very low and has not improved on one medication, for those who have a fracture while on one medication, or for those who have very low BMD and a history of multiple fractures. Further, osteoporosis medication should only be taken in combination on the recommendation of a clinician who specializes in the treatment of osteoporosis.

Although bisphosphonates, estrogen agonists/antagonists, and estrogens all prevent bone breakdown, they do this by different actions. This means that some of them can be taken together. And when taken together, the increase in bone density is greater than if the agents are taken alone. However, some combinations oversuppress bone turnover, increasing the risk for developing "frozen bone,"[1] which means that even though bone mass may increase, the quality of the bone is not good enough to reduce the risk of fractures. Frozen bone may happen when the bone actually becomes more brittle rather than stronger as a result of the action of the medications. For example, taking a combination of Fosamax and Evista or a bisphosphonate and estrogen can increase bone mineral density more than each drug taken separately, but the risk of developing frozen bone due to oversuppression[2] of bone turnover is also present. Since few data are available regarding the effects on fracture with combination therapies, combinations are reserved for certain individuals, as previously noted. Fosamax and estrogen were taken together by a group of post-menopausal women with a hysterectomy[3], while two other groups took one or the other of the two medications. Bone density in the spine and hip increased more in the group taking the combination of therapies than in the groups taking either Fosamax or estrogen alone. However, there was concern that the combination may suppress bone turnover to the point where frozen bone could occur. Similarly, Actonel and MHT also increase bone density when taken individually and taking them together improves bone density even more—however, the quality of the bone remains of concern.

Before deciding with your clinician on a combination approach to preventing and treating osteoporosis, medications should be examined for additional benefits they could provide besides those for your bones. For example, MHT has the benefit of treating the most bothersome symptoms of menopause such as hot flashes, night sweats, and vaginal atrophy. Evista can reduce your risk of breast cancer and heart disease. When taken in combination with bisphosphonates, Evista does not lose these other benefits. However, don't forget that taking two medications means coping with two sets of side effects, the cost of both medications, and potentially negative effects on bone quality.

There are some firm restrictions to using other medications together. Calcitonin nasal spray and bisphosphonates should not be taken together because they may actually oppose one another in their actions. Despite this caution, calcitonin nasal spray is sometimes prescribed following a vertebral fracture for its pain-relieving effects even in those taking bisphosphonates. Forteo (teriparatide) builds bone density when taken by itself, but when taken in combination with Fosamax, bone density does not increase as much as when either agent is taken alone. However, when Fosamax is taken after treatment with Forteo is finished, the improvement in bone density is even greater. So, while taking Fosamax and Forteo together is not helpful, taking Fosamax following treatment with Forteo may provide additional benefit. Again, Evista (raloxifene) and MHT or any estrogen therapies cannot be taken together.

Remember that combination therapy is reserved for individuals whose bone mass is very low and has not improved on one medication, for those who have a fracture while on one medication, or for those who have very low BMD and a history of multiple fractures—and then only on the recommendation of a specialist. The American Association of Clinical Endocrinologists (AACE) advises against using medications in combination with one another until the results of using combinations are analyzed for their effect on fracture risk. The National Osteoporosis Foundation (NOF) recommends caution and carefully considering potential benefits when combining therapies due to the unknown effects of combining medications on fracture risk, increased cost when using two medications, and potential increase in side effects.

  • [1] Speculated to be a potential concern in individuals taking combinations of osteoporosis medications. While the medications increase bone mass, the bone quality may not be as good, resulting in bone that is more brittle rather than stronger.
  • [2] Occurs when bone turnover is suppressed to such a high extent that bone quality may be compromised; associated with "frozen bone."
  • [3] Removal of the uterus.
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