Update on Osteroporosis

UPDATE ON OSTEOPOROSIS

Robert A. Baldor, MD

[Edited for legibility- Last updated 24 November 2006]

Introduction

Confusion exists over the appropriate prevention and treatment of osteoporosis. This has been brought on by the controversy over the safety of hormone replacement therapy (HRT), now referred to as hormone therapy (HT).[1]

The development of newer medications and the availability of office-based screening methods for bone density add to the confusion. Several speakers at the 2003 American Academy of Family Physicians (AAFP) Annual Scientific Assembly in New Orleans covered these issues, including understanding risk factors, prevention, and treatment.

Background

Osteoporosis is a skeletal disease characterized by loss of bone mass and architectural integrity, leading to increased fragility of bones and subsequent risk for fracture. Osteoporosis is often undetected until a fracture occurs.[2] The spine, hip, and wrist are the most common sites for fractures. The lifetime risk of a 50-year-old woman for osteoporotic fracture approaches 40%.

The US Preventive Services Task Force (USPSTF) notes that "One-half of all postmenopausal women will have an osteoporosis-related fracture during their lives, including 25% who will develop a vertebral deformity and 15% who will suffer a hip fracture."[3] This translates into over 1 million fractures annually in the United States.[2]

Many of these women will be subsequently disabled by chronic back pain. Hip fractures are more worrisome, as the subsequent mortality rate is approximately 25% for those greater than 65 years of age. The other common site for fracture, the wrist, causes additional morbidity. While the medical consequences of osteoporosis range from pain to mortality, it can also result in an increased need for long-term care placements as disability limits the ability for self-care.

Diagnosis

Several common methods can measure bone density, including dual-energy x-ray absorptiometry (DEXA), single-energy x-ray absorptiometry, quantitative CT, and quantitative ultrasonography of the heel.[2] DEXA has been the most extensively validated method and is, for many, considered to be the gold standard for assessing bone mineral density (BMD).

Studies have been conflicting and demonstrate that the diagnosis of osteoporosis can vary depending on which area of the body is screened (ie, hip, lumbar spine, forearm, or heel). Furthermore, it is not clear that a low "T" score on a hand or forearm test correlates with increased risk for hip fracture. The USPSTF found that the DEXA of the hip is the best predictor of hip fracture but that bone density measurements of the hand, wrist, forearm, and heel also can be used to detect risk for osteoporotic fracture to some degree.[3,4]

Medicare Part B includes coverage for BMD testing for individuals older than 65 every 2 years if they are estrogen-deficient women who are at clinical risk for osteoporosis, or to monitor response to US Food and Drug Administration (FDA)-approved osteoporosis drug therapy.[4]

It is noted that DEXA reports can be difficult to read, as they provide both a T-score and a Z-score.[2] The T-score is the number of standard deviations above or below the mean BMD for sex- and race-matched young adults ("mean peak bone mass"). The Z-score compares the patient with a population matched for sex and race as well as age[2] (less than 1 standard deviation below mean peak bone mass). Z-scores have not been standardized for clinical practice.

The World Health Organization (WHO) has suggested that osteoporosis exists when bone mineral density (BMD) is 2.5 standard deviations or more below the mean for healthy young adult women at the spine, hip, or wrist (corresponding to a T-score lower than or equal to -2.5).[4] Osteopenia is defined by a T-score between -1.0 and -2.5; a normal T-score is -1.0 and higher.[4]

Primary osteoporosis is related to the aging process, and older women are at a higher risk than younger women partially because of the increased risk for falling due to other medical conditions.[2,3,5] Chronic conditions, such as hyperthyroidism, renal disease, cancer, and hyperparathyroidism, can lead to accelerated bone loss and associated secondary osteoporosis. Risk Factors

Risk factors can be classified as "modifiable" and "nonmodifiable".[2] Nonmodifiable factors among women include female sex, ethnicity (white and Asian), advanced age, family history (fracture in first-degree relative), prior fracture in adulthood, and poor health/dementia with frailty. Emphasis should be placed on identifying modifiable risk factors. Among women, these include smoking, thinness (< 127 lb), early menopause (< 45 years of age, either natural or surgical), excessive alcohol intake (chronic alcohol use inhibits osteoblast function), sedentary lifestyle (those who are physically active earlier in life have a higher peak bone mass at menopause) low calcium intake (women who diet frequently may have limited their intake of dairy products over the years), and poor general health. Recurrent falls and poor eyesight increase the risk for subsequent fracture and should be addressed when assessing the patient.

Chronic use of corticosteroids, thyroid replacement therapy, anticoagulants, or anticonvulsants also increases the risk for osteoporosis as these agents have a detrimental effect on bone metabolism.[2]

When doing an osteoporosis evaluation, the clinician should focus on identifying modifiable risk factors; assessing the patient's physical status, including weight; obtaining a BMD (see below); and formulating a fracture assessment.[2] If the history or physical examination suggests a secondary cause of osteoporosis, a laboratory assessment, including thyroid-stimulating hormone, parathyroid hormone, calcium, vitamin D, complete blood count, chemistry panel, cortisol stimulation test, and erythrocyte sedimentation rate, should be considered.

Screening Strategies

Disagreement exists about which women should be screened and when they should be screened.[3-6] The AAFP recommends measuring BMD in women at increased risk for osteoporotic fractures at 60-64 years of age,[7] in agreement with USPSTF recommendations and similar to the National Osteoporosis Foundation's recommendations to measure BMD for those postmenopausal women younger than 65 years who have risk factors for osteoporosis (other than being white, postmenopausal, and female).

All 3 agree on screening women aged 65 and older. Many physicians rely on the 2002 USPSTF update on screening for osteoporosis in postmenopausal women for guidance.[3] Those recommendations note that osteoporosis and the risk for fracture increase with age; that BMD measurements can determine risk for fracture; and that treating asymptomatic women who have osteoporosis reduces risk for subsequent fracture.

The USPSTF rates its recommendations based on the evidence as outlined in the Table. In its update, the Task Force highlighted the controversy that exists in determining who is at the highest risk for osteoporosis. It concluded that all women should be screened with a bone density test at the age of 65 years ("B" rating) and those at high risk (which could include those weighing less than 154 lb or not using estrogen) starting at the age of 60 ("B" rating). The USPSTF makes no recommendations for or against screening patients younger than 60 years of age or those in the 60- to 65-years age group if not at increased risk ("C" rating). Once osteoporosis has been diagnosed, no further screening is necessary, although additional testing may be required to monitor treatment.

Table. USPSTF Recommendations and Ratings[3]

The USPSTF grades its recommendations according to 1 of 5 classifications (A, B, C, D, or I), reflecting the strength of evidence and magnitude of net benefit (benefits minus harms):

A. The USPSTF strongly recommends that clinicians routinely provide [the service] to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms.

B. The USPSTF recommends that clinicians routinely provide [the service] to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.

C. The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.

D. The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.

I. The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that [the service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined.

Treatment Strategies

There are 3 goals of management:

(1) to stop or reverse bone loss
(2) to increase or stabilize bone mass, and
(3) to reduce fractures, pain, disability and mortality.

However, while most of the focus is on treating osteoporosis, it needs to be emphasized that BMD peaks at about age 35 and then begins to slowly decline with significant acceleration after menopause. Therefore, the most logical and cost-effective preventive strategies are to encourage young women to stop smoking and avoid excessive use of alcohol. They should also be counseled to exercise regularly and consume adequate amounts of calcium and vitamin D.

Nonpharmacologic Therapy and Fracture Prevention[2]

Ensuring adequate dietary calcium intake can be difficult if the patient does not consume a significant amount of dairy products, which are the primary source of calcium. Supplementation is advisable for women whose dietary intake is inadequate.[2] Calcium comes as a citrate or a carbonate formulation. Citrate is best absorbed on an empty stomach while the carbonate preparations should be taken with meals. Iron decreases absorption of calcium; thus, iron supplements should be taken at a different time of the day than the calcium.

Four hundred to 800 IU of vitamin D daily are needed for adequate calcium absorption; 15 minutes of sunlight on the face and forearms is usually sufficient for the body to generate adequate amounts of its own vitamin D.[2] However, the sun's rays above 45° latitude are too weak in winter to generate that degree of vitamin D. Individuals in those regions and institutionalized individuals who do not receive daily sun exposure, for example, could benefit from vitamin D supplementation. Optimal results can be achieved by taking a daily multivitamin in combination with a calcium supplement.

For elderly women who want to reduce their osteoporotic fracture risk, the advice is similar to that for younger women.[2] Physical activity is clearly beneficial, not just because of its positive influence on bone mass but also because those who exercise regularly have improved balance and strength and are less likely to fall. Postmenopausal women are recommended to take 1500 mg daily of calcium supplementation; those who are taking HT are advised to take 1 g per day.[2] Other ways for elderly patients to prevent fracture include focusing on fall prevention strategies by safety-proofing the home by removing scatter rugs, installing safety bars in bathrooms, and using night lights at bedtime. Canes and walkers should be encouraged for those with gait disturbances, and attention should be paid to prescription and over-the-counter medications that may cause lightheadedness or otherwise interfere with balance. Finally, regular eye examinations to ensure adequate vision with updated glasses prescriptions can help decrease the risk for falls.[2]

Pharmacologic Therapy

A number of other pharmaceutical agents, which can be classified as antiresorptive agents or bone-forming agents, are available for treating women with osteoporosis.[2] Antiresorptive agents include estrogens, selective estrogen-receptor modulators (SERMs), the bisphosphonates, and calcitonin. Parathyroid hormone stimulates bone formation. Studies have shown that it can increase bone density in the lumbar spine. It needs to be administered via subcutaneous injection. Teriparatide was approved by the FDA in December 2002 for the treatment of osteoporosis in postmenopausal women who are at high risk for fracture and for men with primary or hypogonadal osteoporosis at high risk for fracture. Fluoride supplementation also stimulates bone formation but does not decrease risk for fracture. It has not been approved by the FDA for osteoporosis prevention and treatment. Indeed, higher doses of fluoride seem to increase the fragility of bone.

Hormone Therapy (HT)

HT has been used for a number of years because it has been demonstrated to increase BMD with subsequent prevention of fractures. The term hormone therapy has been suggested as a substitute for hormone replacement therapy because these medications do not replace the patient's normal hormones. For years, HT was considered the primary preventive therapy for osteoporosis. Touted as an excellent osteoporotic prevention therapy, it was thought also to have positive preventive cardiac benefits. Concerns over uterine cancer were minimized by the use of combined estrogen/progesterone therapies, and worries about the potential increased risk of breast cancer were minimized.[1] However, this past year saw a rapid decline in the enthusiasm for such therapy.

Concerns over the benefits of HT were raised with the 2002 publication of the Heart and Estrogen/progesterone Replacement Study (HERS) and the subsequent publication of the Women's Health and Initiative Study (WHI).[1,6-10] While the WHI confirmed the reduced risk for osteoporosis with combined estrogen/progesterone therapy, it shocked the medical community by showing that instead of providing cardiovascular protection, risk for cardiovascular disease actually increased in women using the combined HT. Risk for stroke and, as expected, for deep venous thrombosis were also increased. Concerns about the increased risk of developing breast cancer were also cited. The WHI study involved 16,000 postmenopausal women and began in 1992. It was planned to run through the year 2007, but was stopped in July 2002 because of its findings.[8,9] Further analysis of the WHI data focusing on the assumed life-quality improvements was published in 2003 in The New England Journal of Medicine.[11] While demonstrating that combined estrogen/progesterone therapy provides relief of menopausal vasomotor symptoms in some women and a small benefit with regard to sleep irregularities, there were no other benefits related to assumed improvements in health quality such as improved general well-being, vitality, depression, and sexuality.[8]

The WHI conclusions created a void in our armamentarium, and questions remain as to who would benefit most from HT. Benefits of combined estrogen/progesterone exist in the short term to assist women with vasomotor symptoms related to the perimenopausal state.[6,11] Long-term estrogens alone appear to be beneficial in preventing osteoporosis. Whether the benefits of estrogen alone outweigh the harms in women who have had a hysterectomy remains to be fully elucidated. We should have more data from a separate WHI study that is looking at this issue and that is expected to be completed in 2005.

Selective Estrogen Receptor Modulators

The FDA approved tamoxifen and raloxifene in 2000 for the treatment of postmenopausal osteoporosis. These medications are contraindicated in women at risk for deep venous thrombosis. Studies have shown that raloxifene decreases risk for vertebral fracture, but hip fracture reduction has not been studied.[2]

Bisphosphonates

Several bisphosphonates have been approved by the FDA for the treatment of postmenopausal osteoporosis, including alendronate, risedronate, and in May 2003, ibandronate. These medications have been demonstrated to increase BMD and reduce risk for fractures. Alendronate and risedronate are relatively expensive drugs. (Although FDA-approved, ibandronate was not yet commercially released in the United States and pricing information was not available at the time of this writing.) Bisphosphonates are associated with the risk for pill esophagitis; however, this may be modulated with the release of once-weekly regimens. It is important to continue calcium and vitamin D supplements while on these agents.

Warning - Some small percentage of patients using biphophonates will develop serious jaw necrosis requiring surgery and bone transplantation.

Calcitonin

Calcitonin inhibits bone reabsorption by its effect on osteoclasts. It is available as a nasal spray at a recommended dose of 200 IU per day, which corresponds to 1 squirt in each nostril every other day. (It is also available in an injectable preparation.) Research has shown reduction of the risk of new vertebral fractures with the use of the nasal spray in postmenopausal women with osteoporosis.[12]

Conclusions

Deciding who should be treated and with what medication needs to be individualized. The patient needs to be informed of the anticipated benefits and the possible side effects. The BMD T-score can assist in decision making.

Bisphosphonates have been shown to increase bone mass and reduce the subsequent risk for fractures. SERMs and calcitonin are reasonable alternatives that appear to reduce spine fractures. However, these newer agents can be more expensive than older HT regimens. They may also have worrisome side effects, so they must be prescribed thoughtfully. Calcium and vitamin D have been shown to delay the onset of osteoporosis but play a limited role in disease treatment. Deciding on how best to treat patients requires a careful consideration of risks and benefits with an informed patient involved in the decision.

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