Prevention and treatment of osteoporosis: Efficacy of combination of hormone replacement therapy with other antiresorptive agents

Osteoporosis is a debilitating disease characterized by decreased bone mine ral density (BMD) leading to fractures. Prevention of osteoporosis is very important because present therapies do not have the potential to mend damag e to the bone microarchitecture caused by osteoporosis. The first line of p revention and treatment of osteoporosis is hormone replacement therapy (HRT ). All of the approved drugs so far for osteoporosis act as inhibitors of b one resorption; these drugs include HRT, selective estrogen receptor modula tors, calcitonin, and bisphosphonates. The latter two drugs have also been shown to prevent fractures. This article discusses data from nine controlle d prospective clinical studies. Study 1 was designed to assess the efficacy of combined HRT and bisphosphonate in preventing osteoporosis during the e arly stages of menopause. This combined therapy increased the lumbar spine BMD by 10.9% and femoral BMD by 7.3% over 1 yr, compared with 6.8 and 4.0% with HRT alone, and 6.8 and 1.2% with bisphosphonate alone. Study 2 was con ducted on postmenopausal women with established osteoporosis. These results showed a 10.4 and 7.0% increase in BMD in vertebrae and femora, respective ly, compared with 7.3 and 4.8% increases in the HRT group, and 6.8 and 0.9% in the bisphosphonate group. Data from study 3 demonstrated similar findin gs in that the combination of alendronate and HRT also enhanced BMD values. Studies 4 and 5 assessed the efficacy of the combined therapy of HRT and c alcitonin in the prevention of postmenopausal bone loss. Both studies demon strated a significant increase in BMD over and above that observed with eit her HRT or calcitonin alone. Studies 6, 7, and 8 demonstrated that the addi tion of testosterone to estrogen therapy further increased BMD when compare d to estrogen therapy alone, in postmenopausal women. Study 9 demonstrated a synergistic effect on BMD in postmenopausal women, when HRT was coadminis tered with monofluorophosphate. Other combination therapies may also enhanc e BMD (e.g., the combination of alendronate and parathyroid hormone [PTH]). However, some agents either lose their efficacy or have no added effects o n BMD when they are coadministered (e.g., tiludronate and PTH, calcitonin a nd PTH, calcitonin and anabolic steroids). These studies illustrate that in a subgroup of patients (i.e., patients with high bone turnover and/or seve re osteoporosis), specific combination treatments such as I-IRT with bispho sphonates, calcitonin, or androgens (and perhaps also with PTH, fluoride, n itric oxide donors) provide additional beneficial effects over a single-dru g therapy. Whether these combination therapies are more effective than indi vidual drugs in reducing fractures still needs to be determined.