What are the effects of treatments to prevent fractures in postmenopausal women?

BENEFICIAL

Alendronate. Two systematic reviews involving postmenopausal women found that alendronate reduced vertebral and nonvertebral fractures compared with placebo after one to four years.

Risedronate. One systematic review involving postmenopausal women found that compared with control (i.e, placebo, calcium, or calcium plus vitamin D) risedronate reduced vertebral and nonvertebral fractures after four years.

Parathyroid Hormone. One randomized controlled trial (RCT) involving women with prior vertebral fractures found that parathyroid hormone reduced the proportion of women with vertebral and nonvertebral fractures compared with placebo. Another RCT involving women with osteoporosis found that parathyroid hormone plus estrogen reduced vertebral fractures compared with estrogen alone after three years.

Raloxifene. One large RCT involving postmenopausal women with osteoporosis found that raloxifene reduced vertebral fractures compared with placebo, but no significant difference was found in nonvertebral fractures. We found no RCTs examining the effects of other selective estrogen receptor modulators.

LIKELY TO BE BENEFICIAL

Etidronate. One systematic review involving postmenopausal women found that etidronate reduced vertebral fractures compared with control (placebo, calcium, or calcium plus vitamin D) over two years but found no significant difference in nonvertebral fractures.

Calcium Plus Vitamin D. One large RCT involving women 69 to 106 years of age living in nursing homes found that calcium plus vitamin D₃ reduced hip fractures and all nonvertebral fractures after 18 months to three years compared with placebo. One smaller RCT involving women and men 65 years or older found that calcium plus vitamin D₃ reduced nonvertebral fractures after three years compared with placebo but found no significant difference in hip fractures. Another small RCT involving post-menopausal women found no significant difference between calcium plus vitamin D₃ and placebo in hip fractures after two years. The two smaller RCTs may have lacked power to detect clinically important differences.

Vitamin D Analogue (Calcitriol). One systematic review found limited evidence from two small RCTs involving postmenopausal women that calcitriol reduced vertebral fractures after three years compared with placebo.

Calcitonin. One systematic review involving postmenopausal women found that calcitonin reduced vertebral fractures compared with placebo one to five years after treatment but found no significant difference between calcitonin and placebo in nonvertebral fractures.

UNLIKELY TO BE BENEFICIAL

Calcium Alone. One systematic review involving postmenopausal women found no significant difference between calcium supplementation and placebo in vertebral or nonvertebral fractures after one and one half to four years.

Vitamin D Alone. One large RCT involving postmenopausal women and two large RCTs involving postmenopausal women and older men provided no evidence of a difference between vitamin D₃ and placebo in hip, vertebral, and nonvertebral fractures after two to five years.

LIKELY TO BE INEFFECTIVE OR HARMFUL

Hormone Therapy. We found insufficient evidence of benefit but reliable evidence of harm.

One systematic review involving postmenopausal women found that hormone therapy reduced vertebral fractures compared with control. However, another systematic review and two subsequent RCTs involving post-menopausal women found no significant difference in vertebral fractures. Two systematic reviews and two subsequent RCTs provided insufficient evidence about the effects of hormone therapy on nonvertebral fractures. One large RCT, which focused on estrogen plus progestin versus placebo for primary prevention of coronary heart disease in healthy postmenopausal women, was stopped because hormonal treatment increased risks of invasive breast cancer, coronary events, stroke, and pulmonary embolism.

UNKOWN EFFECTIVENESS

Environmental Manipulation. We found no systematic reviews and no RCTs assessing environmental manipulation alone.

Exercise. Three RCTs found no significant difference in falls resulting in fracture after eight months to one year between exercise (advice to walk briskly three times weekly, balance and strength exercises plus walking, or low-intensity exercise plus incontinence care) and control. One small RCT involving postmenopausal women found no significant difference between a two-year back strengthening exercise program and usual care in vertebral fractures over 10 years.

Hip Protectors. One systematic review involving older community-dwelling patients or nursing home residents found no significant difference in hip fractures after six months to two years between hip protectors and no protectors in RCTs where individuals were randomized. However, the review found that hip protectors reduced fractures after 11 to 19 months in RCTs that used cluster analysis. The review found no significant difference between hip protectors and no hip protectors in the rate of other fractures.

Definition

This topic covers interventions to prevent fractures in postmenopausal women. Fractures may be symptomatic or asymptomatic. A fracture is a break or disruption of bone or cartilage. Symptoms and signs may include immobility, pain, tenderness, numbness, bruising, joint deformity, joint swelling, limb deformity, and limb shortening.¹ Diagnosis usually is based on a typical clinical picture combined with results from an appropriate imaging technique. Usually, in trials dealing with osteoporosis, menopause is considered to be present 12 months after the last menstruation.

Incidence

The lifetime risk of fracture in white women is 20 percent for the spine, 15 percent for the wrist, and 18 percent for the hip.² The incidence of postmenopausal fracture increases with age.³ One observational study found that age-specific incidence rates for postmenopausal fracture of the hip increased exponentially after 50 years of age.⁴

Etiology

Fractures usually arise from trauma. General risk factors include those associated with increased risks of falling (e.g., ataxia, medication and alcohol intake, loose carpets), age, osteoporosis, bony metastases, and other bone disorders. Postmenopausal women are at increased risk of fracture because of hormone-related bone loss. Risk factors for fractures in postmenopausal women include increasing age; low body mass index; time since menopause; alcohol consumption; smoking; some endocrine diseases, such as hyperparathyroidism or thyroid disease; and steroid use, among others.

Prognosis

Fractures may result in pain, short- or long-term disability, hemorrhage, thromboembolic disease, shock, and death. Vertebral fractures are associated with pain, physical impairment, muscular atrophy, changes in body shape, loss of physical function, and lower quality of life.⁵ About 20 percent of women die in the first year after a hip fracture, representing an increase in mortality of 12 to 20 percent compared with women of similar age and no hip fracture. One half of previously independent older women become partly dependent after hip fracture. One third become totally dependent.