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Diabetes and Osteoporosis

When we think about long term complications of diabetes, Osteoporosis is not one that comes to mind right away. When we first read the article in Clinical Diabetes by Diane L. Chau, M.D. and Steven V. Edelman, M.D., we decided that you needed to understand your risk factors for developing this public health problem.

First, we need to define just what osteoporosis is. It is a bone condition defined by low bone mass, increased fragility, decreased bone quality, and an increased risk for bone fracture. It is the most prevalent metabolic bone disease in the United States.

The World Health Organization reported that 34-50 % of postmenopausal white women have ostepenia, which refers to any decrease in bone mass below the normal. Both low bone mass conditions increase fracture risks, with osteoporosis having the greater impact.

Osteoporosis is expensive in terms of national spending and because of the cost of fractures due to the disease. The National Osteoporosis Foundation reports that this amount is $13.8 billion per year, and that is expected to double over the next 25 years. Although, it has been historically reported mostly in white women, it does affect people of both sexes and all ethnic groups.

Sadly although men are not thought to suffer from the disease, recent research in The Archives of Internal Medicine 2002;162:2217-2222 by Kiebzak et al found that men who had hip fractures were unlikely (11%) to be worked up for osteoporosis and women were worked up slightly more (27%). The 12 month mortality rate for men was 32% compared to 17% for women.

Second, we look at what precipitates the diagnosis. Osteoporosis is not symptomatic until there is a fracture. One in five women is not diagnosed even after a fracture. Any fracture (except from auto accidents) in a person 20 to 50 years of age is associated with a 74% increase in the future risk of fractures after the age of 50.

It is therefore thought that the true numbers of people with osteoporosis may be underestimated because many women who have minimal trauma fractures are not evaluated for osteoporosis. Add to these statistics the fact that fractures increase with age and this is associated with increased mortality and overall functional decline. During the first year following a hip fracture the mortality rate is 36% for men and 21% for women (only slightly different than the stats in the previous paper cited). For certain groups, such as those with psychiatric disorders, the mortality rate has been reported to be > 50%.

What is the prognosis?

If a person survives a fracture, they face greater risks of having a permanent disability and often require long-term nursing care. The recovery process after a fracture is age-and disease-dependent. Those who are younger and healthy have better outcomes. It is now known that persons with either type 1 or type 2 diabetes are among those people at an increased risk for this disease.

Today, physicians often look at dual X-ray absorptiometry (DXA) to study bone mass. This test is not the perfect diagnostic tool because there are many micro-architectural bone qualities and bone geometries that are not detectable with DXA. Therefore, a comprehensive risk assessment for osteoporosis should reach beyond bone mineral density measurements. This is particularly true when assessing people with diabetes.

Type 1 diabetes has long been associated with low bone density. However, it was unclear until recently whether this caused increased bone fractures. The Nord-Trondelag Health Survey from Norway showed a significant increase in fracture rates among female type 1 diabetic patients compared to nondiabetic female patients. Duration of diabetes appears to play a key role as there is a lower BMD in people who have had diabetes for > 5 years.

In the Iowa Women’s Health Study, women with type 1 diabetes were 12.25 times more likely to report a fracture as compared to nondiabetic women. The mechanism of bone loss in type 1 diabetes is still unknown but there are theories based on animal and cellular models. Insulin-like growth factors and other cytokines may influence diabetic bone metabolism.

Diabetic retinopathy, advanced cortical cataracts, and diabetic neuropathy have all been associated with increased fractures. These are also risk factors for increased falls because of visual impairment and alterations in balance and gait. Due to the fact that type 1 diabetes has a young age of onset when bone mass is being accrued, low bone mass would seem to be a likely complication for type 1 diabetes.

Type 2 diabetes had previously been thought to provide bone protection because it is associated with normal to increased BMD, but this information was not based on prospective controlled large trials.

Risk factors are higher for type 2 diabetes than for the general population because of peripheral neuropathy, possible hypoglycemia, nocturia, and visual impairment. Because many type 2 diabetics are over weight and sedentary, coordination and balance factors that protect people from falls are impaired or not present. Thus patients with a larger body size and relatively high bone mass may have a higher fracture rate.

Bone quality changes may also be affected by microvascular events common to diabetes. The Study of Osteoporotic Fractures confirmed that women with type 2 diabetes experience higher fracture rates in regions of the hip, humerus, and foot than do nondiabetic women. Bone loss has also been observed to be greater in patients with poorly controlled diabetes than in those whose diabetes was in tight control.

Gestational diabetes has not been reported to be associated with bone loss in prospective trials. However, a small study involving Hispanic women with gestational diabetes noted that 40% of the 20 enrolled subjects had CXA-detected bone loss when 3 months postpartum. Advanced age and higher oral glucose tolerance test values during pregnancy may be associated with increased bone loss. Larger prospective studies are needed to confirm these findings.

Prevention

Prevention of osteoporosis requires recognition of populations who are at risk, plus screening programs targeting these populations. Available BMD screening include DXA (central and peripheral), peripheral quantitative ultrasound (QUS), and quantitative computed tomography (QCT). None of these tests alone addresses all of the issues involved in disease assessment.

The NOF recommends baseline BMD screening of all postmenopausal women over 65 years of age and of those under 65 who are at high risk. In addition to screening, attempts should be made to address all potentially modifiable risk factors. If a patient is at increased risk of falling, a comprehensive falls evaluation and gait-training program may be beneficial. Additionally patients at high risk should be advised to wear hip protectors that have been reported to reduce the risk of hip fractures by 60%.

When evaluating for osteoporosis all patients with low trauma fractures should be looked at. All patients should have a comprehensive history and physical exam with a focus on secondary factors for osteoporosis.

The symptoms

Osteoporosis is usually not associated with symptoms. If a review of the symptoms includes weight loss, diarrhea, weakness, persistent bone pain, kidney stones, or other complaints, then a thorough evaluation should be done to identify an underlying illness.

Diseases known to cause low bone mass include intestinal malabsorption, anorexia nervosa, cystic fibrosis, Marfan’s syndrome, chronic renal disease, amenorrhea, hypogonadism, thyroid and parathyroid disease, multiple myeloma, AIDS, liver diseases and vitamin D deficiency, among others. Common standard evaluation includes thyroid function test, comprehensive chemistry panel, 24 hour urine calcium and a bone density test to assess the severity of the disease.

Treatment

Treatment includes calcium and Vitamin D. Exercise can also have clinical benefits. In addition to improvements in bone mass, it also results in improved overall muscle strength, which is important in preventing falls. The exercise program should be designed to help not do damage. For example, people who have vertebral osteoporosis should avoid back flexion exercises, particularly those with weights, because they can increase fractures.

Hormone replacement therapy (HRT) was long thought to be the best treatment for osteoporosis because it improved BMD at the hip and spine by 5% and 2.5% respectively. However, we all know that the use of HRT has come under question and the FDA removed approval of estrogen for treatment of osteoporosis, but did permit estrogen to maintain its indication for the prevention of osteoporosis.

In type 2 diabetic women, combination HRT is limited to low-dose formulations. There is a list of medications to treat this disease. In men androgen replacement has improved BMD, however it can not be used in men with a history of prostate cancer. Raloxifen, a selective estrogen is used for both prevention and treatment of osteoporosis.

Salmon calcitonin is a synthetic polypeptide that duplicates molecular structure of calcitonin found in salmon fish. It has been approved by the FDA for the treatment of postmenopausal osteoporosis. It has been reported that it may cause hyperglycemia. The current treatment recommendations have shifted to the use of bisphosphonates (BPN) as a result of many clinical trials. These showed a marked reduction of 40 to 50% in both spine and hip fractures. There have been no negative reports in large studies regarding the use of BPN’s and diabetes. In the future, parathyroid hormone (PTH), a potent anabolic agent, will soon come to the US market under the name Forteo.

In conclusion

Recognized at-risk patients should be treated to prevent osteoporosis. Those with both type 1 and 2 diabetes are at increased risk for developing an osteoporosis-related fracture. BMD measurements are not foolproof in this population.

All diabetes-related factors should be considered in assessing osteoporosis, and fracture risk reduction should be recommended for diabetic patients. Patients with low-impact fractures or osteoporosis should be offered treatment including both nonpharmacological and pharmacological therapies. If you or someone you care about fits this picture, make sure that you are treated in a comprehensive manner.