The Management of Osteoporosis
In October 2004, the Surgeon General of the US issued a report on osteoporosis1 in which he critically documented that most patients who sustain an osteoporosis-related fragility fracture receive neither general nor specific treatment for osteoporosis.2–5 This includes patients who have had hip fractures, for whom the outcome without intervention is often quite bleak.6–8 On a related topic, several publications have highlighted poor compliance/adherence to osteoporosis therapies.9–14
None of these observations would be surprising were it not for the superiority of therapies for the prevention and treatment of osteoporosis compared with therapies for other disease states, such as dyslipidemia or hypertension. This is clearly a biased comment, but it can be substantiated when the following two points are considered. First, therapies approved by regulatory agencies for the treatment of osteoporosis must demonstrate statistically significant antifracture effectiveness. This requirement for an effect on adverse health outcome (fracture) rather than a surrogate (bone mineral density, BMD) is not required for therapies for dyslipidemia or hypertension, where significant changes in the lipid profile or blood pressure suffice. Second, the oral regimen for therapies to prevent or treat osteoporosis are far more simple than those for the other two conditions mentioned above. The therapies can be prescribed once a day, once a week, or once a month. Intravenous therapies are now available that are delivered once every three months, and will likely soon be available in a once-yearly regimen. Many therapies for the other two conditions require multiple daily dosing and often combination therapy. Even when one adds oral calcium and vitamin D to the treatment regimen, the patient still has to take only one—or perhaps two—tablets a day. Additionally, with osteoporosis medications there is no clear indication for monitoring laboratory studies for subclinical side effects such as muscle, liver, or hematological damage.
This review will cover the indications for intervention with specific therapies, as well as the available therapies. Each of the therapies has been approved following controlled clinical trials in which both the treatment and placebo arms received supplemental calcium and vitamin D. While differences in the amount of calcium and vitamin D exist between the trials, it is generally accepted that the daily oral dose of calcium should be 1,200–1,500mg and that of vitamin D should be 1,000–1,500IU per day; vitamin D3 is generally preferred over vitamin D2, although the argument for this is based on limited data. Additionally, patients at risk for fracture or who have already sustained a fracture need to be advised of the benefits of regular exercise for maintaining muscle strength and balance, and of avoiding bad health habits such as smoking or excessive alcohol consumption.
Who Should Receive Therapy for Prevention of Osteoporosis?
In this context, osteoporosis refers to those persons who meet the World Health Organization (WHO) bone densitometric criteria for osteoporosis 4 or who have already sustained osteoporosis-related (minimal trauma/ fragility) fractures. The ultimate aim of preventive therapy is to prevent fractures, but prevention of bone loss is a necessary prerequisite for this. Bone density accounts for only a limited fraction of a person’s risk for fracture and there are aspects of bone quality that can be adversely affected by minimal changes in BMD. Therefore, it is essential to obtain a complete history to determine whether there are any BMD-independent predictors of fracture.
Many professional organizations have developed ‘discipline-specific’ guidelines for selecting such persons. There is considerable commonality to these numerous guidelines, but it is wise to rely on the guideline most relevant to one’s practice. Many of these BMD-independent risk factors can be determined by history (e.g. family history of fragility fracture or history of substantial corticosteroid use). It must be emphasized that these risk factors for fracture are not predictive of BMD. Recently, a Task Force of the WHO has developed algorithms for the prediction of hip fracture risk based on age, other clinical factors, and BMD factors;15–17 it is likely that these algorithms will be adopted into the guidelines of most related professional organizations throughout the world. These new WHO algorithm-based guidelines should become available during 2008.
Who Should Receive Treatment for Osteoporosis?
Any person in whom BMD measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, proximal femur, or radius (mid-shaft) is 2.5 standard deviations (SDs) below the mean for healthy pre-menopausal white women (T-score <-2.5) has osteoporosis and should be treated. Likewise, any person who has sustained a fragility fracture not due to local pathology (e.g. metastasis) or from a systemic sclerotic bone disease (e.g. osteopetrosis) has osteoporosis and needs therapy.
