New options in osteoporosis therapy: Combination and sequential treatment
Perhaps the biggest medical question to emerge from the WHI study is how to best treat postmenopausal osteoporotic women. Could the answer lie in combining 2 current monotherapies?
A 56-year-old woman presents with a recent bone density demonstrating T-scores of -3.2 at her hip and -2.4 at the lumbar spine. The patient had her last menstrual period at age 53. She experienced vasomotor symptoms for 8 months, but no longer has hot flashes.
Two years ago, her sister, then age 45, was diagnosed with bilateral breast cancer. There is no other family history of this disease. At the time of her sister’s diagnosis, the patient had T-scores of -2.7 and -2.3 at the hip and lumbar spine, respectively. She was prescribed exercise, vitamin D 800 IU, and calcium supplements, as well as raloxifene 60 mg daily to both improve her bone density and reduce her risk of breast cancer.
A case for combination therapy.
During the 2 years of raloxifene therapy, the patient’s lumbar spine bone density stabilized but her hip bone density declined. At this follow-up visit, she underwent a series of tests for secondary causes of osteoporosis (TABLE 2). All results were within the normal range.
In this case, the addition of a second agent such as alendronate (70 mg once weekly) or risedronate (35 mg once weekly) is warranted to reverse the continued bone loss in her hip. It is likely that on combination therapy, her bone density will increase.1 In addition, continued raloxifene treatment will reduce her risk of breast cancer—a major worry of hers due to her sister’s illness.
TABLE 2
Laboratory test results for secondary causes of osteoporosis and osteomalacia
| CONDITION | LABORATORY TEST RESULT |
|---|---|
| Hyperparathyroidism | Elevated parathyroid hormone |
| Elevated calcium | |
| Decreased phosphorus | |
| Vitamin D deficiency | Decreased 25-hydroxyvitamin D |
| Hyperthyroidism | Decreased thyroid-stimulating hormone |
| Renal disease | Elevated phosphorus |
| Decreased calcium |
REFERENCE
1. Johnell O, Scheele WH, Lu Y, Reginster JY, Need AG, Seeman E. Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2002;87:985-992.
- Johnell et al.8 In a clinical trial, 331 postmenopausal women with osteoporosis were randomized to receive placebo, raloxifene (60 mg daily), alendronate (10 mg daily), or raloxifene plus alendronate for 1 year.
A 48-year-old woman became menopausal at age 44. She was a 2-pack-per-day smoker for many years, but recently quit. At the early age of menopause onset, she began therapy with conjugated equine estrogen 0.625 mg daily and medroxy-progesterone acetate 2.5 mg daily. The patient had no hot flashes and no menses with this treatment.
Based on the media coverage of the Women’s Health Initiative results, she recently decided to discontinue hormone replacement therapy. She knows this will result in an accelerated rate of bone loss and wonders what she should do. A bone density test demonstrates T-scores of -2.1 and -2.3 in the hip and spine, respectively. What would you advise?
A case for sequential therapy. In menopausal women, discontinuation of hormone replacement therapy is associated with a rapid loss of bone mineral density.1 Now that this woman with osteopenia has discontinued her estrogen treatment, it is highly likely she will become osteoporotic unless a bone medicine is initiated.
Sequential therapy of hormone replacement followed by a bisphosphonate has been associated with an increase in bone density. For this woman, initiation of treatment with a bisphosphonate—alendronate 70 mg once weekly or risedronate 35 mg once weekly—is indicated to prevent a decline in bone density. In addition, regular exercise, vitamin D, and calcium supplements may help preserve her bone mass.
REFERENCE
1. Greenspan SL, Emkey RD, Bone HG, et al. Significant differential effects of alendronate, estrogen or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. Ann Int Med. 2002;137:875-883.
- Neer et al.9 In 1 clinical trial, 1,637 postmenopausal women with a previous osteoporotic fracture were randomized to treatment with placebo or PTH monotherapy (20 μg or 40 μg daily by subcutaneous injection) for an average of 21 months. PTH treatment increased BMD compared with placebo. New vertebral fractures were documented in 14% of the women receiving placebo and 5% and 4% of women taking PTH 20 μg and 40 μg, respectively. New nonvertebral fractures were documented in 6% of those in the placebo group and 3% of those in each of the PTH groups. Side effects associated with PTH included nausea and headache.
