MJA: Osteoporosis consensus statement, Australia 1997

The prevention and management of osteoporosis
Consensus statement

6: What interventions are effective in preventing osteoporosis and osteoporotic fractures?

Childhood and early adulthood

Achieving a higher peak bone mass is likely to reduce the risk of osteoporotic fracture in later life. Since peak bone mass is achieved by late adolescence or early adulthood, intervention in childhood and adolescence may be important.

Exercise

Several studies suggest that exercise in prepubertal children has positive effects on bone density. Whether benefits achieved before puberty are sustained into adulthood is uncertain, although cross-sectional studies of retired athletes suggest this may occur. In contrast, exercise after puberty appears to have less effect.

Calcium

Dietary calcium supplementation has a small positive effect on bone, mainly in prepubertal children. The effect is small compared with growth-related increases in bone density, and is lost when supplementation stops. From these studies it is not possible to determine what the minimum quantity of calcium required for normal growth is. However, intakes substantially below the current recommended dietary intake (about 900 mg/day) should be avoided. Extremely low intakes of calcium may have irreversible effects on bone mass.

If nutrition is not adequate to maintain normal body weight in childhood and early adulthood, bone density may be lost due to gonadal dysfunction.

Summary

A healthy lifestyle can be advocated in adolescence and early adulthood, including regular exercise, adequate calcium intake and avoidance of tobacco smoking or excessive alcohol intake. There are insufficient data to prove that such interventions will lead to reduction in osteoporosis in later life. The extent to which lifestyle factors in adolescence and early adulthood affect peak bone mass is unknown.

Older adults

General advice

Similar lifestyle changes have also been suggested for the prevention of osteoporosis in adults.

In adults the results of intervention studies to date do not substantiate the notion that calcium supplementation or exercise are effective means of increasing bone mass. Trials using weight training or increasing calcium intake by about 1000 mg/day have achieved differences of 1%-3% in bone mass over about two years. These effects are small in relation to the 5%-10% differential in mass theoretically needed to alter fracture rates by 25%-50%. Whether these results are due to changes in bone mass homeostasis or whether they reflect a continuing effect on loss of bone is unclear. Furthermore, there have been no community-based trials to determine the long-term efficacy or effectiveness of educational programs on fracture rates.

Therefore, while it is reasonable to promote a healthy lifestyle including exercise, no smoking, moderate intake of alcohol and adequate nutrition, exaggerated claims about the effect on bone density or fracture rates should not be made, nor should an impression be given that these measures are as effective in retarding bone loss as some of the drugs used to treat osteoporosis. The effect of exercise on fall reduction may be more important than any effects on bone density (see Question 11).

Specific therapies

Decisions about management depend on the absolute risk of fracture and the potential benefits and adverse effects of alternative treatment options. For those at moderate risk, prophylaxis or intervention should have minimal adverse effects. For those at high risk (e.g., previous fracture, very low bone density) more aggressive therapy is indicated.

Although most fracture studies have been performed in women, the relationship between bone density and fracture is similar in men. Therefore, treatments which increase bone density in women are likely to have equivalent efficacy in men. With all therapies for osteoporosis, it is likely that the beneficial effects on fracture risk are maintained for only a limited period after the treatment is stopped.

Hormone replacement therapy

Hormone replacement therapy has been shown to prevent early postmenopausal bone loss. Long-term therapy (for more than five to ten years) after menopause probably reduces fracture risk, although it may need to be continued indefinitely to show any benefit. In late postmenopausal women, hormone replacement therapy may increase bone density by about 5% above baseline in the lumbar spine over two years. Observational studies have shown its use to be associated with reduced fracture rates throughout the skeleton, and vertebral fractures have been shown to be reduced in randomised controlled trials. There are no data from randomised controlled trials on the effect of hormone replacement therapy on hip fractures.

Hormone replacement therapy has other benefits in postmenopausal women. It relieves urogenital symptoms and may be associated with a reduction in the incidence of cardiovascular disease. It is clear that any effect on the risk of breast cancer is small; evidence on the risk from long-term use (more than five to ten years) is awaited from current prospective randomised studies. The effects on bone density of oestrogen with supplemental calcium may be additive or more than additive.

The extensive documentation on its efficacy and safety make hormone replacement therapy the treatment of choice in postmenopausal osteoporosis.

Bisphosphonates

The early bisphosphonate, etidronate, increases bone density in the lumbar spine by 3%-5% above baseline after two years of therapy in late postmenopausal women, with a reduction in fracture risk. Newer, more potent bisphosphonates may have a better therapeutic profile. Two large randomised three-year studies of one of these, alendronate, found increases in bone density comparable to those seen with hormone replacement therapy, and a reduction in relative fracture risk of about 50%. There is little experience with bisphosphonate use beyond three years of continuous therapy. Their safety and efficacy make the newer, more potent bisphosphonates first line therapy in older individuals unable or unwilling to take hormone replacement therapy.

Vitamin D (calciferol)

Recent studies from a number of countries have demonstrated that vitamin D deficiency is common in the institutionalised elderly due to poor sunlight exposure. Correction of this deficiency reduces hip and other non-vertebral fractures. This intervention involves the use of replacement doses of calciferol (500-1000 units/day or 50 000 units/month). Avoiding vitamin D deficiency in this at-risk group is an important part of providing care for the elderly. The continuing availability of oral formulations of vitamin D is a priority (supplies of vitamin D were difficult to obtain last year, despite being listed on the PBS).

Active vitamin D metabolites (calcitriol)

Calcitriol has a therapeutic profile distinct from vitamin D and should not be used in the treatment of vitamin D deficiency. Calcium supplements should be stopped while using calcitriol.

There is disagreement about the place of active vitamin D metabolites in the management of postmenopausal osteoporosis. One study showed a reduced fracture rate with calcitriol, while other, smaller, studies with limited power did not. Calcitriol may be more effective in people with reduced efficiency of calcium absorption. These uncertainties should be resolved by further large randomised controlled trials. However, calcitriol may have a major role in the management of glucocorticoid-induced osteoporosis. In patients commencing glucocorticoids, calcitriol has been shown to prevent spinal bone loss.

Calcium

Long-term high calcium intake in postmenopausal women appears to prevent or reduce loss of bone, resulting in a 1%-3% difference in bone density compared with untreated individuals over two years. Several small studies in the elderly have suggested there may also be a reduction in the number of fractures after taking calcium supplementation. Although calcium intake by itself is less effective than hormone replacement therapy or other therapies, adequate calcium intake should be part of routine management. The target total intake should be about 1500 mg/day in those not using more effective treatments. Dietary and supplemental forms of calcium appear to be equally well absorbed, with no need for additional components for effective absorption other than normal vitamin D status.

Other agents

Anabolic steroids (e.g., nandrolone decanoate) are testosterone analogues. A number of randomised controlled trials have shown moderate increases in spinal bone mineral density. However, data regarding their antifracture efficacy are inconclusive. Their long-term use in effective doses is accompanied by a high incidence of side effects.

The use of fluoride should be restricted to research and specialist centres.

Calcitonin is an antiresorptive agent used in some parts of the world for treating osteoporosis. Its expense, side effects and difficulties with administration mean that it is not widely used in most countries.

Hip protectors have been shown in one randomised controlled study to halve the rate of fractures in the institutionalised elderly, although compliance may be poor.

Alternative therapies

In the community, a variety of alternative therapies, such as phytoestrogens, herbal medicines and nutritional additives, are used for osteoporosis. Currently, there is no evidence that these agents have any benefit and this would need to be established by randomised controlled trials. Their cost and potential side effects must be considered.

Effectiveness of interventions in reducing osteoporotic fractures

Strategies that reduce the risk of fractures overall do not guarantee that osteoporotic fractures will not occur. This is not surprising, as even the most effective interventions for improving bone density, if applied late in the osteoporotic process, do not return bone mass to young normal levels. Rather, they slow down the loss or effect a modest increase in bone density. Since some untreated individuals at risk will not sustain a fracture anyway and therefore will not benefit from treatment, any interventions (drug or non-drug) requiring long-term application must be safe, efficacious and free of serious side effects. The total cost of all such interventions, including diagnostic testing, monitoring and costs for the community or the individual, must be included as part of any cost-benefit evaluation.

The availability of safe and effective therapies for osteoporosis raises questions about whom they should be offered to. The cost-benefit analysis of a decision to treat is heavily influenced by the likelihood of fracture. If an intervention halves fracture risk, a large number of fractures will be prevented if it is used in a population with a high baseline risk of fracture.

This effect can be quantified by determining the number of individuals needing to be treated in order to prevent a fracture, as set out in Box 4.

4: Number needed to treat for three years to prevent one fracture.

a Risk of any fracture in unselected women aged 60 to 80 years.
b Risk of any fracture in postmenopausal women with bone density T-score < -2.5.
c Risk of vertebral fracture in women with a pre-existing vertebral fracture.

This figure is based upon results of the two large randomised controlled trials of alendronate, and data from the Dubbo Osteoporosis Epidemiology Study. The higher the pretreatment fracture risk, the smaller the number needed to treat to prevent a single fracture. The dotted lines on the x-axis of the figure indicate the baseline fracture risk of different population groups (highest in those with previous fracture and lowest in unselected normal subjects). The most cost effective use of resources is to intervene in those with pre-existing fractures, though intervention in lower risk groups may also be justified depending on the cost and safety of the intervention.

Next: When should low bone density be treated?

Title page - Contents list - Register to be notified of new articles by e-mail - eMJA home page - Top of page