Overview

Osteoporosis is a common disease characterized by the loss of bone mass (thinning of bones) that leads to an increase in bone fragility and heightened risk of fractures, especially at the hip, spine and wrist. The National Osteoporosis Foundation reports that in the U.S., approximately 10 million individuals already have osteoporosis and an additional 34 million have low bone mass (also known as osteopenia), placing them at an increased risk of developing osteoporosis. The International Osteoporosis Foundation reports that osteoporosis affects an estimated 75 million people in the U.S., Europe and Japan.

While women are at greater risk of osteoporosis, men also can develop the condition. Risk factors include family history, age, postmenopausal status, low dietary calcium intake, sedentary lifestyle and use of certain medications such as corticosteroids. As life spans increase globally, the number of individuals at risk of osteoporosis will continue to rise. At age 50, approximately one in two women and one in four men can expect to have an osteoporosis-related fracture during the remainder of their lives, with the risk increasing with age. Fractures resulting from osteoporosis can be painful and debilitating, compromising the quality of patients’ lives and in the case of hip fractures, increasing the risk of institutionalization, disability and early mortality.

The International Osteoporosis Foundation reports that osteoporosis affects an estimated 75 million people in the U.S., Europe and Japan.

Prevention of Osteoporosis

Diet and exercise can help prevent osteoporosis. The dietary calcium found in such foods as dairy products, oil-rich fish and some vegetables and soy products, along with regular weight-bearing exercise, can help individuals build and maintain their bone mass, ideally beginning early in life. Avoidance of smoking and excessive alcohol consumption is also advised. When dietary calcium intake is insufficient, calcium and vitamin D supplements are recommended. For more information on osteoporosis prevention, consult your physician.

Physiology of Osteoporosis

The skeleton is a large dynamic organ that accounts for approximately 15% of the weight of a young adult and is the principal organ to store elemental calcium in the body. The levels of calcium in the blood are tightly regulated because of the key role calcium plays in many important bodily functions. If calcium levels are too low, the body releases parathyroid hormone to break down bone and release calcium; conversely if calcium levels are elevated the thyroid gland releases calcitonin to inhibit bone breakdown and the kidneys increase excretion of calcium into the urine.

Throughout life the bones comprising the skeleton turn over (known as remodeling) every six to 10 years. During this process old bone is removed by cells called osteoclasts and new bone is synthesized by cells called osteoblasts. This process serves to keep bones healthy, allowing micro-fractures and other small defects to be repaired. Under normal physiologic conditions there is a balance between the amount of bone removed and the amount of new bone synthesized. This balance in bone breakdown and bone synthesis is disrupted in people with osteoporosis, in whom bone loss exceeds newly synthesized bone, resulting in a net loss of bone mass. Without intervention, over time the amount of bone loss can become substantial, leading to porous, fragile, easily fractured bones.

Diagnosis of Osteoporosis

Osteoporosis and osteopenia (low bone mass) are diagnosed using a specific X-ray format called DEXA (dual energy x-ray absorptiometry) that measures bone mineral density. DEXA is relatively easy to perform and the amount of radiation exposure is low. At present, DEXA scanning focuses on two main areas – the hip and spine. Although osteoporosis involves the whole body, measurements of BMD at one site can be predictive of fracture risk at other sites. Scanning generally takes 10 to 20 minutes to complete and is painless. As individuals lose bone, their BMD as measured by DEXA decreases. Once the decrease in BMD reaches a predetermined level, or T score, (defined as 2.5 standard deviations below a healthy young woman’s peak BMD), the individual is diagnosed as having osteoporosis.

Osteoporosis Treatment Options

There are two main categories of osteoporosis treatments: anti-resorptive drugs intended to prevent further bone loss and anabolic bone-forming drugs that stimulate development of new bone:

Anti-resorptive drugs act as modulators of osteoclast activity to slow bone turnover and thereby reduce bone loss from the skeleton. Anti-resorptive drugs are the most commonly used and include calcitonins, bisphosphonates and selective estrogen receptor modulators (SERMS). The FDA has also approved an injectable monoclonal antibody-based drug, Prolia® (denosumab), for the treatment of postmenopausal women who already have osteoporosis and face a high risk of fracture and to increase bone mass in men with osteoporosis at a high risk of fracture. Hormone replacement therapy (HRT) while indicated for the prevention of osteoporosis, is used substantially less today than in the past, due to the potential for serious side effects.

Anabolic (bone-forming) drugs, acting on osteoblasts, the bone-forming cells, are generally indicated only for patients with more severe osteoporosis. The marketed product in this class is teriparatide, a form of parathyroid hormone that is approved for the treatment of osteoporosis in postmenopausal women and in men who are at high risk because they already have fractures or have taken steroid medicines for a long time. Teriparatide must be injected daily; its duration of use is limited to two years due to a reported carcinogenic effect in rats.

Potential safety issues with current drug therapies, while rare, have led ~4 million women to discontinue therapy since 2008, while other osteoporosis patients are reluctant to initiate treatment. According to the International Osteoporosis Foundation, studies indicate that up to half of osteoporosis patients stop their treatment after just one year. In one study, two-thirds of osteoporosis patients said their medication interfered with their lives in some way and over 20% of the women who missed or stopped their treatment said it was due to side effects. A recent journal article reported that prescriptions for oral bisphosphonates, the most commonly used class of drugs for the treatment of postmenopausal osteoporosis, fell by 53% between 2008 and 2012 (Wysowski et al., J Bone Min Res 2013).

With so many osteoporosis patients abandoning or not initiating drug therapy due to safety concerns with existing treatments, and few new drugs reaching the market, the number of untreated patients has soared. Over time untreated osteoporosis will result in more individuals suffering disabling fractures, with negative effects for individuals, their families, and society as a whole.