Osteoporosis and Inflammatory Bowel Disease

Issue: January 2017

Osteoporosis, or “thinning of the bones,” is a concern among many women, especially those who are experiencing or have experienced menopause. Osteoporosis increases one’s susceptibility to developing fractures of the bones in the wrist, ribs, vertebral spine and hips, often with minimal trauma. Osteoporosis accounts for 1.5 million fractures and results in more than $13 billion in medical costs in the United States annually. It is estimated that more than 5 million U.S. citizens have osteoporosis, and more than 21 million have a precursor condition called osteopenia. Although postmenopausal white women are at highest risk for osteoporosis and osteopenia, these conditions are occurring with increasing frequency in men and non-white women.

Risk Factors

Numerous studies show patients with inflammatory bowel disease (IBD), especially Crohn’s disease (CD), are at increased risk for osteoporosis and osteopenia. Some population-based estimates suggest osteoporosis may occur in as many as one in seven patients with CD, while osteopenia may occur in as many as 45%. No single reason explains why IBD is a risk factor for osteoporosis.

Possible explanations for osteoporosis in patients with IBD include the following:

Corticosteroids, such as prednisone, have been known for years to have powerful effects on bone metabolism. Studies show decreased bone density and increased fracture risk may occur within a few months of starting steroids. Even low-dose prednisone (5 mg daily) usage has been associated with an increased fracture risk.
Other drugs, such as cyclosporine and methotrexate, may reduce bone density slightly.
Inflammatory bowel disease itself, especially CD, may be a risk factor. Low bone densities have been noted in newly diagnosed patients, even before they have received corticosteroids. It is thought that perhaps elevated levels of circulating inflammatory cytokines have negative effects on bone formation and resorption.
Patients with CD with small bowel involvement, or with a history of small bowel resections, may not properly absorb calcium and/or vitamin D.
Many patients with IBD have a low BMI, which is an independent risk factor for osteoporosis.
Cigarette smoking is a risk factor for osteoporosis, and many patients with CD have a history of former or current smoking.
It is important to note the most important risk factors for osteoporosis in the general population — older age, female gender and low body mass index — are also the most important predictors of osteoporosis in the IBD population.

Low bone mineral density does not necessarily correlate exactly with fracture risk, so it is important to determine whether patients with IBD have an increased risk of fracture. Most studies of fracture risk in IBD suggest patients with IBD are 15% to 45% more likely than the general population to develop an osteoporotic fracture (hip, spine, wrist or ribs). In most — but not all — studies, the fracture risk seems slightly higher in CD. It is interesting to note the smaller studies (ie, a few hundred patients) have not demonstrated an increased fracture risk, while the larger studies (ie, a few thousand patients) have. In other words, we can reassure patients that although their fracture risk is increased, it may not be as high as previously thought.

Who to Screen

If the risk of fracture is elevated in IBD, how do we decide which patients should be tested for osteoporosis? Blanket screening of all patients with IBD would probably result in unnecessary testing. The IBD patients most at risk for fracture are postmenopausal women, patients with low BMI and those receiving steroids. Guidelines from several gastroenterologic societies recommend that dual-energy X-ray absorptiometry (DXA) scanning be performed in IBD patients with one or more of the following risk factors: older than 60 years; low BMI; heavy smoking history; postmenopausal; steroid treatment for at least 3 months; recurrent courses of steroids; and a history of prior fractures.

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Fracture Risk Assessment

The results of a DXA scan are usually given as a T-score. The T-score indicates the standard deviation from the mean peak bone mass in the general population. In other words, a score of –3 indicates the patient’s bone density is 3 standard deviations below the mean, while a score of 0 indicates a bone density exactly at the mean. A patient is considered to have osteoporosis if the T-score in the lumbar spine, hip or wrist is below –2.5, while osteopenia is defined as a T-score between –1 and –2.5.

Treatment of Osteoporosis

The following measures can be used to treat IBD-associated osteoporosis.

Lifestyle modifications, such as regular exercise and cessation of cigarette smoking, should be encouraged.
Elemental calcium intake should be at least 1,200 mg/day. For patients who do not ingest this amount of calcium in their diet, a calcium carbonate or calcium citrate supplement should be recommended.
Vitamin D intake should range from 400 IU to 800 IU daily. Higher levels may be required in patients with malabsorption or vitamin D deficiency. Such deficiency should be corrected prior to treatment with a bisphosphonate.
Strong consideration should be given to the use of IBD medications that allow steroid-dependent patients to wean successfully off steroids. Examples include azathioprine, 6-mercaptopurine, methotrexate and anti-tumor necrosis factor inhibitors.
Estrogen seems to be falling out of favor after one study showed the risks of increase in cardiovascular events and breast cancers outweigh the benefits of combined estrogen-progestin therapy. However, selective estrogen-receptor modulators, such as raloxifene, may increase bone density and reduce fracture risk, but not at the cost of an increase in breast cancers.
Bisphosphonates, which block bone resorption, can be administered. Two oral bisphosphonates, alendronate and risedronate, which can be given on either a daily or a weekly basis, have been shown to increase vertebral and femoral neck bone density and reduce vertebral and hip fractures for both postmenopausal and glucocorticoid-induced osteoporosis. In addition, risedronate prevents bone loss in patients receiving corticosteroids. Ibandronate can be given orally on a daily or monthly basis, or given intravenously (IV) every 3 months, and has also been approved by the FDA for the prevention and treatment of postmenopausal osteoporosis. It has been shown to increase bone mineral density and decrease fracture risk with a superiority for the IV formulation. Gastrointestinal adverse events, including esophagitis, may occasionally occur with oral administration of any of these medications, necessitating other treatment alternatives.
Pamidronate, 60 mg IV every 3 months to 6 months, has been used by some physicians to deliver bisphosphonates for those who cannot tolerate oral preparations. Zoledronic acid (5 mg IV/year) is FDA-approved for the prevention and treatment of both postmenopausal and glucocorticoid-induced osteoporosis, as well as the treatment of osteoporosis in men.
Nasal calcitonin-salmon spray also has been shown to be effective for improving bone density and reducing fracture risk in the lumbar spine, primarily in women who are older than 5 years postmenopausal.
Recombinant parathyroid hormone, or teriparatide, when administered subcutaneously on a daily basis, can improve bone density and reduce fracture risk significantly. However, because of the observation of osteosarcomas in laboratory rats following the administration of this drug, the FDA has suggested its use be limited to patients for whom the potential benefits are considered to outweigh the potential risk (ie, patients with a previous history of osteoporotic fracture, multiple risk factors, or who have failed or are intolerant to other treatments), and it is contraindicated in children and adolescents.

By following the guidelines presented herein, we can identify patients with IBD at risk for osteoporosis, use a noninvasive screening tool to test them, and then choose an agent to reduce their future risk of fracture. Preventing a complication is always easier than treating one.