Treating Osteoporosis: Raloxifene

A post hoc analysis of data from this study showed daily raloxifene reduced the risk of clinical vertebral fractures at 1 year by 68% (P <.05) in the overall population and 66% (P < .05) in women with a baseline vertebral fracture. (54)

The incidence of nonvertebral fractures was similar with raloxifene or placebo in the overall study group. However, in a post hoc analysis, those with a severe vertebral fracture at baseline (> 40% decrease in vertebral height) had a 47% reduction (P = .046) in overall nonvertebral fracture risk after 3 years of daily raloxifene.(55)

Adverse Effects of Raloxifene
Daily raloxifene is associated with an increased incidence of influenza syndrome, hot flashes, leg cramps, and peripheral edema compared with placebo.(53) It is also associated with a higher risk of thromboembolic events, with rates similar to those reported for postmenopausal women receiving estrogen therapy.(56)

Salmon Calcitonin
Salmon calcitonin nasal spray reduced the 5- year risk of new vertebral fractures by 33% (P = .03) in postmenopausal women with vertebral fractures at baseline at the approved daily dose of 200 IU (but not at 100 IU or 400 IU) vs placebo.(57) It did not reduce the risk of nonvertebral fractures, including hip fractures. The dropout rate was 59% over 5 years and was similar in all treatment groups. Salmon calcitonin nasal spray was generally well tolerated, but a slight increase in rhinitis was reported in treated patients vs placebo.

Teriparatide
Teriparatide, a formulation of recombinant human parathyroid hormone (1-34), induces bone formation. In contrast, the other agents inhibit bone resorption.

In a study in 1,637 postmenopausal women with at least one vertebral fracture, teriparatide (20 µg subcutaneously once a day) reduced the risk of new morphometric vertebral fractures by 65% (P <.001) and of nonvertebral fractures by 35% (P = .04) over a median follow-up of 21 months. (58) The risk of nonvertebral fractures considered to be fragility fractures was reduced by 53% (P = .02).

Dizziness and leg cramps were reported in significantly more patients with teriparatide treatment than with placebo. (58)

The US Food and Drug Administration recommends the use of teriparatide for no more than 2 years, as clinical data are available for only 21 months. (59)

Hormone Therapy
The Women's Health Initiative trial found that hormone therapy reduced the risk of hip and spine fractures.(60) However, risks associated with hormone therapy may be greater than previously thought, (61) and it should be used only as long as is necessary to treat menopausal symptoms.

Combination Therapy
In theory, it is possible that combinations of different medications may confer additive or synergistic benefits. However, recent data indicate that alendronate blunts the effects of teriparatide, (62,63) so these two agents should not be used simultaneously.(64) More studies are needed to determine whether different combinations of medications are beneficial.(65)

Case Revisited
In our patient, who has severe osteoporosis and multiple risk factors, once-daily or once weekly bisphosphonate therapy is recommended as first-line therapy to reduce fracture risk.

Teriparatide is a reasonable alternative if she has a poor response (see below) or does not tolerate either bisphosphonate. Its appropriate role is still evolving. It may be useful as initial therapy followed by an antiresorptive agent (ie, a bisphosphonate) in patients at high risk.

Raloxifene and salmon calcitonin are other alternatives, but neither has reduced the risk of nonvertebral fractures in postmenopausal women with osteoporosis in prospective studies.

Hormone therapy is not indicated for the treatment of postmenopausal osteoporosis, and therefore it is not an option for this patient.

Follow-Up DXA for Patients on Therapy
Depending on the coefficient of variation of the particular DXA device used, an improvement of less than 2% per year would be considered a nonresponse.

The frequency of repeated DXA determinations depends on the severity of the initial measurement. For most patients, repeated DXA every 2 years allows enough time between measurements to allow significant expression of change of bone density. But if a patient has severe osteoporosis with fractures or has secondary causes such as steroid exposure or hyperparathyroidism, then yearly or even more frequent determinations may be warranted.

Cleveland Clinic Journal of Medicine
Volume 71, Number 10, October 2004

The author has indicated that he has received grant or research support from the Wyeth, Pfizer, Proctor and Gamble, Sanofi, NPS, and Alexis corporations and is on the speakers' bureaus of the Abbott, Merck, and Proctor and Gamble corporations. This paper discusses treatments that are experimental or are not approved by the US Food and Drug Administration for the use under discussion.