Given the prevalence of osteoporosis, these authors offer a primer on noted risk factors and pertinent insights on treatment options ranging from exercise and nutrition to pharmacologic interventions.

After years of extensive studies, it has become clear that a healthy skeletal system plays a vital role in one’s overall health and quality of life.1,2 Despite this realization, an estimated 10 million Americans over the age of 50 have osteoporosis while another 34 million are at risk. Each year, an estimated 1.5 million people experience an osteoporosis-related fracture that, in many cases, leads to a rapid decline in physical and mental health, which often results in death within one year.

Given these issues, it is evident that osteoporosis and its comorbidities have a significant impact on mortality, morbidity and medical expenditures. As the population ages, the burden of osteoporosis will likely increase and further strain an already significantly, economically challenged health care system.



Fortunately, there have been many scientific advances in our understanding of the prevention, diagnosis and treatment of this disease. These advances encourage us to believe we are now in a strategic position to significantly reduce the risk of developing osteoporosis as well as related fractures and other comorbidities.

Understanding Key Risk Factors And Clinical Features of OP
In order to facilitate preventive efforts in high-risk patients and early recognition of the disease process, it is important to have a strong grasp of the key metabolic and clinical features associated with osteoporosis.
Bone is constantly undergoing turnover. One usually achieves peak bone mass by the age of 20 and this is determined by several factors that include genetics, race, nutrition, calcium/vitamin D intake, exercise and hormones. Bone is normally remodeled through an interdependent process involving both active bone formation and breakdown (ie, resorption), which normally keeps the bone mass constant. At the cellular level, new bone formation is mediated by osteoblasts while bone resorption is mediated by osteoclasts.3

Clinically, fractures are the most important consequence of osteoporosis and are a major health issue among the elderly. Currently, in women, more osteoporotic-related fractures occur per year than the cumulative number of heart attacks, stroke and breast cancer. Osteoporosis develops when osteoclast activity becomes more predominant than osteoblastic activity and results in a reduction in skeletal mass. Researchers have identified the loss of gonadal function and aging as key contributors to this imbalance.4

There are two types of osteoporosis. Primary osteoporosis accounts for 80 percent of the cases but has no identifiable cause. The prevailing thinking is that estrogen deficiency in women (often referred to as postmenopausal osteoporosis) and age are believed to be important factors. Primary osteoporosis is associated with increased rates of both bone resorption and formation, with the bone resorption predominating. Secondary osteoporosis is involved with bone loss that is associated with an identifiable cause (e.g., other diseases, drugs, immobility).

Risk factors for osteoporosis include advanced age, female gender, Caucasian or Asian race, and a personal or family history of fracture.

Osteoporosis is regarded as a silent disease because there are usually no symptoms for patients until a fracture occurs. However, recent advances point to key risk factors associated with early osteoporosis and the subsequent identification of high-risk individuals that should undergo diagnostic testing.2,4

Risk factors of osteoporosis include advanced age, female gender, Caucasian or Asian race, and a personal or family history of low trauma induced fracture. Modifiable risk factors include cigarette smoking, malnutrition, lactose intolerance, alcohol, caffeine or protein abuse, and physical inactivity.2 When it comes to osteoporosis, high-risk individuals include:

• all women the age of 65 and over regardless of risk factors;
• younger postmenopausal women with one or more risk factors (other than being Caucasian, female and postmenopausal); and
• men and postmenopausal women who present with fractures.4

All of these high-risk patients should undergo bone mineral density testing in order to establish the diagnosis and determine the severity of the disease.4

Essential Principles In Managing Osteoporosis
The main goal in treating osteoporosis is preventing fractures. In general, other goals include maintaining bone health by preventing bone loss and building new bone.

For treatment, the recent comprehensive, multidisciplinary United States Surgeon General Report on bone health recommends utilizing a pyramid approach.1 The base of the pyramid (level 1) applies to all individuals whether or not they have low bone mass or multiple risk factors for fracture, and focuses on lifestyle changes directed at maintaining bone health and preventing fractures. It is recommended that everyone at this level should: strive for adequate levels of calcium and vitamin D intake; engage in regular weightbearing exercises; avoid behaviors that impair bone health (e.g., cigarette smoking); and understand how to avoid falls.

The authors emphasize the role of patient education in facilitating compliance with treatment regimens for osteoporosis. Two key areas are promoting an awareness of factors that influence bone health and explaining medication use and adverse effects when appropriate.

The second level of the pyramid applies to patients at high risk for fractures. At this level, one must determine whether there are secondary causes or aggravating factors (e.g., drugs) in the development of osteoporosis and consider the possible need for non-pharmacologic interventions and pharmacologic treatment.3

The third level of the pyramid involves pharmacologic options for osteoporosis. In general, there are two types of drug therapy for treating this disease. One approach utilizes anti-resorptive agents to reduce bone loss while another approach involves using anabolic agents to stimulate bone production.3

After establishing a diagnosis of osteoporosis, it is essential that the patient understand the course of the disease as well as the pharmacologic and non-pharmacologic options. Given the heterogeneous nature of OP, it is important to realize that one must tailor the treatment course to the individual patient. A strong interaction between the treating clinician and the patient will help facilitate selection of the best evidence-based treatment that balances benefits and risks.

The guiding principle in managing osteoporosis is reducing the probability of fractures while controlling the pain, disability and associated mortality. Clinicians can accomplish this by decreasing bone loss, preserving or increasing bone strength and restoring bone mass to maximum levels.
For individuals who have low bone mass but no fractures, clinicians should emphasize aggressive preventive measures using proper nutrition and regular physical activity. When a patient already has one or more fractures, employing additional and more aggressive interventions is indicated to prevent new fractures.
Clinicians should vigorously inform all patients of universal strategies for preventing osteoporotic fractures. These strategies include: fall prevention strategies (e.g. adequate lighting, securing area rugs); a hip protector for patients with an increased propensity for falls; and discussing the importance of smoking cessation, weight-bearing exercises and calcium/vitamin D enriched and well-balanced diets.

Fortunately, there are a variety of treatment strategies for osteoporosis. Non-pharmacologic options include calcium and vitamin D supplementation as well as other lifestyle changes. Pharmacologic options include hormones (calcitonin, parathyroid hormone fragment (PTHf)), selective estrogen receptor modulators (SERMs), bisphosphonates and estrogen under special circumstances. With the exception of PTHf, which functions as an anabolic agent that stimulates osteoblast bone formation, all of the other agents work by reducing bone resorption via the inhibition of osteoclast activity. All of these agents, with the exception of estrogen, can also increase bone mineral density (BMD) and reduce biochemical markers of bone turnover.

Can Calcium And Vitamin D Supplements Have An Impact?
Calcium and Vitamin D are essential in childhood skeletal development and in the maintenance and achievement of optimum bone mass in adults.1 The recommended daily intake of calcium is 1200 mg for men and women over the age of 50. Calcium carbonate is effective and the least expensive calcium supplement while the more expensive calcium citrate is tolerated better by patients who have gastrointestinal distress.
Since vitamin D is essential for the absorption of calcium from the gastrointestinal tract and for assimilation into bone, one should emphasize supplementation at the daily dose of 200 to 600 IU. Deficiency of vitamin D can lead to impaired calcium absorption, secondary hyperparathyroidism and decreased bone mineral density. It also may result in neuromuscular coordination difficulties leading to an increased risk of falls. Deficiencies usually occur secondary to inadequate sunlight exposure and inadequate dietary intake. Serum levels of 25-hydroxyvitamin D greater than 20 mg/ml are usually considered normal.

It is important to note that calcium and vitamin D supplementation alone may slow but not prevent bone loss in postmenopausal women.

How Can Calcitonin Be Beneficial?
Calcitonin (Miacalcin) is a polypeptide hormone produced by the thyroid gland in response to elevated serum calcium levels. It is involved with decreasing serum calcium levels as it decreases bone resorption and increases urinary calcium excretion. Calcitonin also slows bone loss by directly inhibiting osteoclasts. It also has analgesic properties that are likely secondary to the release of endogenous opioids.5-7

Calcitonin is effective in reducing vertebral fractures and can increase lumbar bone mineral density. However, it is ineffective in preventing or reducing hip fractures and does not increase femoral bone mineral density. Due to these limitations, clinicians usually reserve calcitonin for treating postmenopausal osteoporosis in patients who are unable to tolerate the gastrointestinal effects of bisphosphonates.6 Clinicians also commonly utilize calcitonin for pain relief associated with acute fracture. The nasal formulation is usually preferred.7

Does Estrogen Therapy Have A Role?
In the past, a number of studies have shown that estrogen replacement is an effective therapy for preventing and treating postmenopausal osteoporosis.4,8,9 Estrogen/progestin therapy is effective in reducing vertebral and hip fractures. However, estrogen/progestin therapy does not increase lumbar and femoral bone mineral density. It also increases the risk of breast cancer, heart disease, stroke and deep vein thrombosis (DVT).
Based on this risk/benefit ratio, the FDA currently recommends that clinicians only prescribe estrogen when the benefits outweigh the risks.

Selective estrogen receptor modulators (SERMs) represent a new class of drugs approved for the prevention and treatment of postmenopausal osteoporosis.4,10,11 These agents have different effects on specific estrogen receptors throughout the body. These include some benefits of estrogen (e.g. increased BMD, decreased serum lipids) without the side effects (e.g. breast tenderness, menstrual abnormalities, breast cancer).

Raloxifene (Evista) has been designed to preserve bone density without increasing breast cancer risk. Raloxifene is effective at decreasing vertebral fractures as well as elevating lumbar and femoral bone mineral density.4 Most interestingly, raloxifene lowers total and LDL cholesterol. However, it does not relieve vasomotor symptoms and may increase hot flashes.

A Closer Look At Teriparatide
Teriparatide (Forteo) is a peptide fragment of parathyroid hormone (PTHf). Teriparatide affects calcium and phosphorous metabolism in much the same manner as endogenous PTH. It binds to osteoblasts and increases intracellular production of cAMP by adenyl cyclase which, in turn, stimulates osteoblastic activity. This anabolic agent is very effective in reducing both vertebral and non-vertebral fractures, as well as increasing lumbar and femoral bone mineral density.4,5,12-14

In order to maintain bone health and prevent fractures, experts emphasize the preventive value of regular weightbearing exercises, striving for adequate levels of calcium and Vitamin D intake, and avoiding behaviors like smoking that impair bone health.

Teriparatide, a daily injectable drug, is approved for treating postmenopausal women and men with primary or hypogonadal osteoporosis who are at high risk for fracture. It is important to note that the FDA currently limits the use of teriparatide to two years and there is a black box warning due to an increased incidence of osteosarcoma in rodents.12

A Guide To The Benefits Of Bisphosphonates
Bisphosphonates are effective in slowing bone mass loss as they decrease bone turnover and increase bone formation. They primarily inhibit osteoclast life span and resorptive activity. Each of the bisphosphonates is very effective in decreasing hip and vertebral fractures while increasing lumbar and femoral bone mineral density. Consequently, they are approved for prevention and treatment of osteoporosis in postmenopausal women, osteoporosis in men, and the prevention and treatment of glucocorticoid induced osteoporosis in men and women.4,8,15-26

These agents (alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva)) are currently available in once-daily or once-weekly doses with ibandronate approved for a convenient single monthly dose.15,20,25 (See “A Primer On Biphosphonates For Osteoporosis” on page 16.) It is anticipated that using these high-dose, once-weekly/once-monthly formulations will improve inherence, which is a major problem.

Supplementing bisphosphonate therapy with calcium and vitamin D is recommended. Most recently, the combination Fosamax (alendronate) plus D and Actonel (risedronate) with Calcium became available. Two clinical trials have studied alendronate and risedronate for the treatment of osteoporosis and both studies suggest increased effectiveness for alendronate.16,19

Keep in mind that bisphosphonates have low oral bioavailability and can cause gastrointestinal inflammation and ulceration. Therefore, clinicians should advise patients to take bisphosphonates on an empty stomach with a glass of water and remain in an upright position for 30 minutes.4

Combination Therapy: What You Should Know
Due to the success of the different types of osteoporosis therapies and their different mechanisms of action, there have been questions about the potential of combining these agents and whether the combination would be better than monotherapy.

While there are not many current studies available to answer this question, researchers have shown that some combinations increase bone mineral density better than either agent alone. These combinations include hormone therapy and bisphosphonates; raloxifene and alendronate; and parathyroid hormone and hormone replacement therapy.4 Based on these preliminary studies, this area warrants further investigation.

How To Combat Poor Adherence
Retrospective longitudinal studies provide compelling evidence that adherence to osteoporosis therapies is poor. These studies indicated that the mean duration of therapy for discontinuation of daily bisphosphonates was 139 days and 239 days with weekly bisphosphonates.27

Accordingly, clinicians should emphasize patient education in several key areas in order to facilitate improved inherence. They should:

• promote an awareness of factors that influence bone health;
• identify patients at risk of bone
disease;
• educate patients on lifestyle and therapeutic interventions to prevent bone loss and fractures;
• educate patients on nutrition and physical activity;
• ensure proper screening;
• explain medication use and adverse effects when appropriate;
• monitor treatment compliance and develop strategies to maximize adherence; and
• emphasize fall prevention.

Final Notes
Healthy bones play a vital role in overall health and a patient’s quality of life by providing the body with a frame that allows for mobility and protection of vital organs, and serving as a storehouse for essential minerals that help maintain life sustaining physiologic homeostasis and longevity. On the other hand, unhealthy bones perform these functions less effectively, ultimately leading to debilitating fractures and subsequent increased mortality.

Currently, the overall bone health status of Americans appears to be suboptimal. Given the aging population and the previous lack of attention on bone health, it is estimated that the number of hip fractures in the US could double by the year 2020.1

However, recent advances in our understanding of key risk factors associated with the condition, the importance of prevention and the emerging developments in treatment can aid health professionals who routinely see these patients. By proactively assessing, diagnosing and treating at-risk patients, health professionals are in a position to make a significant impact on bone health.

When it comes to preventing and treating osteoporosis in postmenopausal women, bisphosphonates are effective in slowing bone mass loss as they decrease bone turnover and increase bone formation.