Osteoporosis is a disease of the bones that affects both men and women. It can lead to fractures, morbidities, and--indirectly--mortality. Many prevention and treatment options are available, allowing treatments for individual patients to be optimized. This article focuses on prevention and treatment and on how pharmacists can promote good bone health.
Osteoporosis is the most prevalent of the bone diseases. It is generally recognized as a woman's disease, affecting primarily postmenopausal Caucasian and Asian women. Less commonly, osteoporosis can occur in men and women of any age and race who have risk factors (TABLE 1). It is a clinically diagnosed problem in approximately 10 million Americans over 50 years of age, 80% of whom are women. Another 34 million people with low or decreasing bone mass are progressing toward a diagnosis of osteoporosis.1 An estimated 1.5 million fractures per year are related to osteoporosis, with hip, vertebral, and wrist bones being most commonly involved.2 In 2002, an estimated $12 to $18 billion--not including productivity losses--was spent on osteoporosis-related fractures. Since the average age of the U.S. population continues to increase, the incidence of osteoporosis is expected to rise also.1 Women have a 50% chance of an osteoporosis-related fracture in their lifetime after age 50, and the risk of a second fracture increases dramatically after the first occurrence. Hip fractures are indirectly linked to mortality, and although women are more likely to suffer a hip fracture, men have a higher incidence of mortality within 1 year after the event.2
Osteoporosis is a disease characterized by decreasing bone density or mass, which weakens the bones and skeleton. There is a change in the microarchitecture of the bone, and there comes a point when the rate of bone resorption exceeds the rate of bone formation. There are many risk factors for osteoporosis (TABLE 1). The disease is caused primarily by normal age-related changes, but it can be worsened by hormones, poor nutrition, diseases, or medications.3 The most common form of the disease is postmenopausal osteoporosis. Postmenopausal women are at greater risk because they can lose up to 20% of their bone mass in just a few years owing to loss of estrogen after menopause.2
Osteoporosis has been labeled a silent disease because it is usually asymptomatic until a fracture occurs and diagnostic tests are performed. Rarely, some patients may present with back pain or developing kyphosis (rounded back) in the setting of vertebral fractures.3 The National Osteoporosis Foundation (NOF) has recently updated its recommendations for risk assessment and screening to work with the World Health Organization (WHO)'s fracture risk-assessment tool (FRAX).4,5 The WHO FRAX algorithm (see Resources box) can be used to predict the 10-year risk of hip and other major osteoporotic fractures in previously untreated patients, but has not been studied in patients with low vertebral bone mass.4,5 For the assessment of risk, the NOF suggests an extensive evaluation of the patient's risk factors, history, and bone mineral density (BMD). Testing of BMD is suggested by the NOF for postmenopausal women, all women over age 65, all men over age 70, and men aged 50 to 70 with related risk factors.4
The standard of diagnosis is a dual-energy x-ray absorptiometry (DXA) scan of the hip and spine areas. Portable ultrasound machines that estimate BMD of the heel, forearm, or fingers are commonly used at pharmacies and health fairs. These modalities are meant to be used as screening tools. Spinal or peripheral CT-based absorptiometry tests can be used to predict risk as well, but these methods expose the patient to significantly more radiation than the DXA scan and have not been shown to be useful in men.4 The results of these bone tests--a T-score or Z-score--are reported as a standard deviation from a database population. The T-score compares the patient's BMD with that of a young healthy person of the same sex; the Z-score includes age and ethnicity.1,4 The WHO defines osteoporosis as a T-score of less than -2.5 at the hip or spine. A score between -2.5 and -1 is defined as low bone density or high risk, and a score above -1 is considered healthy.6
Osteoporosis is a preventable disease, and numerous prevention therapies are available, ranging from lifestyle modifications to vitamin and mineral supplementation to medications. Most prevention strategies are cost-effective ways to promote bone health and reduce risk.
Lifestyle modifications are the easiest interventions and can be safely recommended to most patients. Reduction of risk factors can be initiated by increasing calcium and vitamin D intake, performing weight-bearing exercise, quitting smoking, avoiding excessive alcohol consumption, and preventing falls. Although no definitive recommendations for exercise regimens have been developed, a combination of strength training and weight-bearing exercises can be suggested that will meet an individual's needs.4
Lifelong adequate calcium intake is the most reliable way of maintaining bone health. Assessing daily dietary intake of calcium is the first step and the first-line strategy. Dairy products are the best source, although numerous prepared food products are fortified with calcium, vitamins, and other minerals. Greens and sardines are some nondairy sources. Calcium supplements should be used only when the diet is insufficient or inconsistent.4
The average person over the age of 50 typically gets less than 700 mg of calcium per day from dietary intake.4 At least 1,200 mg of elemental calcium per day is recommended for women and men aged 50 years and over; 1,000 mg per day is recommended for those aged 19 to 50 years with no risk factors; and 1,300 mg per day is recommended for those aged 9 to 18 years.1 A recent meta-analysis showed that fracture risk was reduced by 12% in patients (primarily women) over the age of 50 when they took at least 1,200 mg of calcium alone or 1,200 mg of calcium with 800 IU of vitamin D daily. The risk reduction was 24% when populations with compliance rates of 80% or more were considered.7 The upper intake limit for calcium is 2,500 mg per day, but more than 1,200 mg to 1,500 mg per day has not been proven effective and may increase the risk of adverse events.1,4 Calcium absorption is best in carbonate or citrate form, but is inefficient and unreliable when more than 500 mg at a time comes from these supplements or fortified foods.1
Calcium absorption and excretion are dependent on many nutrients, including phosphorus, magnesium, fluoride, and--most importantly--vitamin D.1 Vitamin D is a major component of many different functions of the body and can be synthesized in the skin from sunlight (ultraviolet) exposure, although the body's ability to do so decreases with increasing age. Vitamins D2 and D3 can be obtained in the diet from fortified foods and saltwater fish, but this is rarely sufficient to provide adequate amounts for older patients.8 Therefore, it is recommended that adults over the age of 50 and those who are otherwise deficient take 800 IU to 1,000 IU of vitamin D2 or D3 per day.4 Vitamin D levels can be measured by serum 25-hydroxyvitamin D (25OHD) concentrations; the desirable level is 30 ng/mL or 75 nmol/L.4,9 One study showed that 25OHD levels of 86 nmol/L in postmenopausal women increased calcium absorption by 65% compared with levels of 50 nmol/L.9
Magnesium is another important nutrient involved in maintaining bone health. It is supplied in adequate amounts by a well-balanced diet of vegetables, whole grains, and nuts. The North American Menopause Society (NAMS) suggests that taking magnesium supplements to protect bone health should be considered only in patients with increased magnesium loss (due to gastrointestinal disorders and vomiting), since evidence is controversial as to the bone-density benefit in postmenopausal women.10 Some calcium supplements, multivitamins, and bisphosphonates are combined with vitamin D, magnesium, and other minerals to enhance absorption and encourage adherence.
Only a few of the prescription medications approved for the treatment of osteoporosis are also approved for prevention. Alendronate, ibandronate, and risedronate are the approved bisphosphonates for postmenopausal osteoporosis prophylaxis. Estrogen/hormone therapy and raloxifene--an estrogen agonist/antagonist, or selective estrogen receptor modifier (SERM)--are other options indicated for prevention.11
In transitioning from prevention to treatment, the recommendations change very little. Risk factors still should be reduced or avoided when possible, dietary intake of calcium and vitamin D should remain adequate, and adherence to drug therapy should be encouraged. Determining whether to treat a patient with prescription medications should be based on clinical judgment as well as patient history, risk factors, and BMD estimates.4 Treating other underlying diseases is also a critical step for preventing fractures. When deciding on a treatment regimen, considerations should include expected adherence, understanding of the disease, and affordability.4
Bisphosphonates: The medications in this class act by inhibiting osteoclast activity and reducing the rate of bone turnover. The bisphosphonates are most commonly used for prevention and treatment, and are considered first-line therapy for the treatment of postmenopausal women (TABLE 2).10 In almost all studies of bisphosphonates, the patients were concurrently obtaining adequate calcium through supplementation or diet.8 Individual agents differ in dosing schedules and available formulations. All FDA-approved agents have been shown to be beneficial. The safety and BMD associated with the various dosing schedules appear to be similar, although there are no conclusive data regarding the incidence of fractures based on these dosing frequencies. Choosing an agent may depend on patient preference. Adherence counseling is especially important because bisphosphonates are generally known to be difficult to administer.
Alendronate and risedronate are available as daily, weekly, or monthly tablets. Alendronate also comes packaged in combination with vitamin D; risedronate also is available in combination with calcium carbonate. Alendronate has been shown to decrease the incidence of vertebral, hip, and wrist fractures in patients with and without a prior vertebral fracture.12,13 Risedronate has been found to decrease the rate of vertebral and other fractures in patients with a prior vertebral fracture.14,15 Ibandronate is available as daily or monthly tablets and as a quarterly injection; it has been found to reduce vertebral fractures.16,17 Zoledronic acid, which is available as a yearly infusion, has been shown to reduce vertebral, hip, and other fractures.18
Estrogen/Hormone Therapy: For a long time, estrogen replacement therapy was the standard treatment for postmenopausal women needing osteoporosis prophylaxis. Estrogens with or without progestin are known to have a positive effect on bone health, but the numerous side effects and potential risks have limited use to prevention of postmenopausal osteoporosis.11 Patients with a uterus should take estrogen with progestin to reduce the risk of endometrial cancer. Estrogen both alone and in combination with progestin increases the risk of myocardial infarction, stroke, and deep venous thrombosis (DVT). More common, less serious side effects include breast tenderness and hormonal changes.4 Current treatment options with less risk now exist; therefore, risk versus benefit should be considered before therapy is initiated, and the lowest dose should be used for the shortest possible duration when needed.4 The NOF, WHO, and NAMS suggest that estrogen therapy be reserved for patients unable to take other nonestrogen therapies.4,6,10
Raloxifene: This is the only SERM approved for the prevention and treatment of osteoporosis, although other SERMs are being developed and studied.10,19 Raloxifene 60 mg once daily has been found to decrease the risk of vertebral fractures over 3 years, and it is suggested for use in patients with a greater risk of vertebral fracture than hip fracture.4,10 Raloxifene works as an estrogen agonist in some areas of the body and antagonistically in uterine tissue, reducing the potential for cancer.11 There is a risk of DVT and coronary heart disease, and hot flashes and muscle cramps are the most frequently reported adverse events.4,11 Patients taking raloxifene should discontinue use 72 hours prior to prolonged immobilization owing to the risk of adverse events such as DVT or stroke. Use with cholestyramine (decreased absorption) is not suggested. Caution is recommended with warfarin because concurrent use can decrease prothrombin time.19
Calcitonin: Calcitonin is a synthetic polypeptide hormone created from the calcitonin of salmon, which is more potent than human calcitonin. It should be reserved for patients who cannot take or tolerate estrogens and women who are at least 5 years postmenopause. Calcitonin was studied in combination with adequate calcium and vitamin D for up to 2 years' duration.20 Salmon calcitonin nasal spray (200 IU per spray) is approved as a daily single-spray inhalation for the treatment of postmenopausal osteoporosis. Intramuscular and subcutaneous injection forms (100 IU daily, every other day, or 3 times per week) are available as well.11 Since there is the possibility of allergic reaction or anaphylaxis with administration, test dosing may be necessary. Common side effects include rhinitis, epistaxis, sinusitis, and headache.20 The injectable dosage form may cause local site reactions, flushing, skin rash, pruritus, and fever.11 Counseling for the more commonly used nasal spray (Miacalcin) should include storing unopened bottles in the refrigerator, allowing the spray to come to room temperature before use, priming the pump prior to use, alternating nostrils daily, and storing the bottle at room temperature after opening.20
Parathyroid Hormone: Teriparatide is a recombinant human parathyroid hormone approved for treating osteoporosis. It acts as an anabolic agent, increasing bone mass when given daily. A subcutaneous injection of 20 mcg once daily for no more than 2 years is currently recommended for decreasing the risk of both vertebral and nonvertebral fractures.4 There is no evidence of the safety and efficacy of teriparatide after 2 years, and an increased incidence of osteosarcoma in rats has been demonstrated at a much higher systemic dose than the indicated human dose. Risks should be weighed when teriparatide therapy is being considered, and its use should be avoided in patients already at risk for bone cancers, including individuals with Paget's disease, history of bone metastases, or history of radiation to the bones. Drug interactions are rare; side effects are limited but include leg cramps, dizziness, and injection-site reactions. Teriparatide is available as a prefilled pen (Forteo) that should be stored in the refrigerator. Counseling should include instruction on subcutaneous administration into the thigh or abdomen.21 Current prescribing habits involve using teriparatide for 2 years, then initiating a bisphosphonate or other antiresorptive treatment.4
The best thing a pharmacist can do is to recognize patients at risk and recommend lifestyle modifications to prevent osteoporosis. The importance of lifelong adequate calcium intake, physical activity, and risk-factor reduction for maintaining bone health is something a pharmacist should stress for the whole family. It is important to identify patients on drug therapy whose intake of calcium, vitamin D, and magnesium is inadequate. It may be necessary to suggest vitamin and mineral supplementation.
Combining drug classes for osteoporosis treatment may provide small increases in BMD, but clinical evidence of decreased fracture rates has not been shown. The additional cost, side effects, and risks should be considered before recommending multiple treatments.4
Adherence to osteoporosis therapies has been notoriously poor. A meta-analysis of the data published between 1990 and 2006 determined that one-third to one-half of treated patients were not taking their medication as directed.22 Since there are no obvious indicators of treatment efficacy, monitoring practices suggest follow-up bone scans every 2 years after initiation of therapy and whenever deemed medically necessary.4
Osteoporosis prevention can begin at a very early age. Good nutritional habits are always beneficial. As our population grows older and the incidence of postmenopausal osteoporosis increases, the focus can shift to prevention of fractures and research into more efficacious and safer therapies. Proper education of the public, combined with early initiation of treatment, can help reduce the incidence of complications in most women.
1. U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General; 2004.
2. National Osteoporosis Foundation. Fast facts on osteoporosis. www.nof.org/osteoporosis/
3. Lindsay R, Cosman F. Osteoporosis. In: Kasper DL, Braunwald E, Fauci AS, et al. Harrison's Principles of Internal Medicine. 15th ed. New York, NY: McGraw Hill Professional; 2001:2226-2237.
4. National Osteoporosis Foundation, in collaboration with American Association of Clinical Endocrinologists (AACE), American College of Radiology (ACR), American Osteopathic Association (AOA), International Society for Physical Medicine and Rehabilitation (ISPRM). Clinician's Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2008.
5. World Health Organization Collaborating Centre for Metabolic Bone Diseases. Fracture risk assessment tool. www.shef.ac.uk/FRAX. Accessed February 26, 2008.
6. WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Level. Summary Meeting Report: Brussels, Belgium 5-7 May 2004. Geneva, Switzerland: World Health Organization; 2007.
7. Tang BM, Eslick GD, Nowson C, et al. Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet. 2007;370:657-666.
8. In a conversation with R. P. Heaney, MD (February 2008).
9. Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. 2003;22:142-146.
10. Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause. 2006;13:340-367.
11. Clinical Pharmacology [database online; subscription required]. Tampa, FL: Gold Standard, Inc; 2008. www.clinicalpharmacology.com. Accessed February 11, 2008.
12. Fosamax (alendronate sodium) package insert. Whitehouse Station, NJ: Merck and Co, Inc; February 2008.
13. Fosamax Plus D (alendronate sodium/cholecalciferol) package insert. Whitehouse Station, NJ: Merck and Co, Inc; February 2008.
14. Actonel (risedronate sodium) package insert. Cincinnati, OH: Procter & Gamble Pharmaceuticals, Inc; April 2008.
15. Actonel With Calcium (risedronate sodium with calcium carbonate) package insert. Cincinnati, OH: Procter & Gamble Pharmaceuticals, Inc; January 2008.
16. Boniva (ibandronate sodium) package insert. Nutley, NJ: Roche Laboratories Inc; August 2006.
17. Boniva Injection (ibandronate sodium) package insert. Nutley, NJ: Roche Laboratories Inc; February 2007.
18. Reclast (zoledronic acid) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corp; June 2008.
19. Evista (raloxifene hydrochloride) package insert. Indianapolis, IN: Eli Lilly and Co; December 2007.
20. Miacalcin (calcitonin-salmon) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corp; June 2006.
21. Forteo (teriparatide [rDNA origin]) package insert. Indianapolis, IN: Eli Lilly and Co; February 2008.
22. Kothawala P, Badamgarav E, Ryu S, et al. Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin Proc. 2007;82:1493-1501.
Acknowledgment: The authors would like to thank Robert P. Heaney, MD, for his comments and suggestions.To comment on this article, contact firstname.lastname@example.org.