A 57 y/o post-menopausal female patient presents to your clinic and requires treatment for osteoporosis. A recently ordered bone density scan shows a T score of >(-) 2.5. She is Caucasian, of slight build, a non-smoker, exercises very little, and receives moderate sun exposure tending to her garden. She has no other significant medical history and is on no other meds. She has no or minimal post-menopausal symptoms (hot flushes etc).

The medical student wants to treat this patient aggressively using both raloxifene and alendronate. His rationale is with her T score and other risk factors, dual drug therapy (using two drugs with different mechanisms of action) will more quickly reverse or stop the osteoporosis and prevent fractures.

Do you concur with the student? Why or why not?

 ** THANKS to MR Dave Bretzke, PEC pharmacist/data dude for his help with this Pearl.**

This patient should take the other steps in addition to whatever prescription medication(s) you give to her. Minimize her alcohol use. Decrease caffeine in the diet. Exercise (esp weight bearing) is beneficial in preventing osteoporosis. Adequate dietary intake of calcium and Vitamin D is a must. Daily intake of calcium should be between 1,000 and 1,500 mg per day of elemental calcium. Vitamin D should be ~ 400 I.U. per day for women between 50 and 70 years of age.

The 'final' word on dual therapy is not known yet. Current thinking is to NOT use dual therapy.

Although combination therapy (raloxifene and alendronate) makes intellectual sense and has increased bone mineral density compared to either agent alone, the possible 'excessive' suppression of bone turnover may pose a safety concern. High bone turnover before treatment increases fracture risk. Associations have been reported from observational studies between low bone turnover and increased fracture risk. Animal studies showed high doses of biphosphonates (ex. alendronate) are associated with suppression of bone turnover, accumulation of microdamage, and deficiencies in bone material properties. Significant decrease in bone turnover ("frozen bone") may actually lead to increased fractures. Bisphosphonates have long half-lives in bone and may inhibit remodeling to the extent damage is NOT repaired. Combination therapy (i.e. adding raloxifene) that suppresses bone turnover even more might further contribute to this problem. Further controlled studies are needed to more accurately define this risks and benefits of combination therapy for osteoporosis.

The American Association of Clinical Endocrinologists 2001 guidelines for the prevention and treatment of postmenopausal osteoporosis states, "No data firmly establish that the combined use of two antiresorptive agents (for example, bisphosphonates plus ERT or raloxifene; estrogen plus calcitonin) has an additive effect on fracture reduction. Additive effects on bone mass and bone turnover have been observed. Until the effect of combined therapy on fracture risk is understood, however, AACE does not recommend concomitant use of these agents for prevention or treatment of post-menopausal osteoporosis." (Endocrine practice 2001;7:293-312)

REFERENCES:

- Marcus R, Wong M, Heath H, Stock JL. Antiresorptive treatment of post-menopausal osteoporosis: Comparison of study designs and outcomes in large clinical trials with fracture as an endpoint. Endocrine reviews 2002;23:16-37

- Johnell O, Scheele WH, Lu Y, et al. Effects of raloxifene, alendronate, and raloxifene and alendronate on bone mineral density and biochemical markers of bone turnover in postmenopausal women with osteoporosis. J Bone Mineral Res 1999;14:S157.

- Bone HG, et al. Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/estrogen study group. J Clin Endocrinol Metab 2000;85:727-33.

- Wimalawansa SJ. Combined therapy with estrogen and etidronate has an additive effect on bone mineral density in the hip and vertebrae; four year randomized study Am J Med 1995;99:36-42.

Obviously, one would perform a thorough physical exam and more in-depth history. Other precipitants of loss of control would be evaluated and ruled in or out. Ipratroprium [Atrovent®] metered dose inhaler (MDI) contains an ingredient in the formulation similar to soya lecithin or food products such as soybean and peanut. Atrovent® MDI (not the nebulizer solution) is CONTRAindicated in patients with a hypersensitivity to any of these agents.

Treatment will depend on the severity of the reaction. Stopping the Atrovent® would be a good first step. Steroids, nebulized b agonists, SQ epinephrine, etc may be indicated. Long-term maintenance may now include inhaled steroids, leukotriene antagonists, etc.

Dr Hoeben asks anyone possessing a list of medications containing any type of food component(s) in them, to email it or the web address to her at Barbara.hoeben@lakenheath.af.mil.