Unlike the study of rosiglitazone that led to new FDA warnings, both of these studies were observational, rather than being randomized clinical trials. Only a randomized trial (in which participants are randomly assigned to one of the treatments being compared) can eliminate the influence of factors that might make a person more likely to receive one treatment over another in a real-world situation. Since people who take thiazolidinedione drugs may tend to be different in unknown ways from those who do not, an observational study cannot determine the effect of these drugs on BMD with any statistical certainty.
The role of diabetes
Numerous explanations have been suggested for the effect of diabetes on BMD and risk of fracture, but so far, most are not backed up by conclusive research. They include hormonal factors such as higher insulin levels, diabetic complications, and a higher rate of falls. In most studies of both Type 1 and Type 2 diabetes, level of blood glucose control has not been associated with BMD or risk of fracture, but more research is needed to confirm this finding.
One possibility currently under investigation is whether advanced glycation end-products (AGEs), substances that are formed when glucose reacts with proteins inside a cell, accumulate in bone tissue and weaken it. New evidence is also emerging that connects BMD to some conditions that commonly arise from diabetic complications: Very recent studies suggest that reductions in nerve, kidney, and cardiovascular function are related to lower BMD, bone loss, and fracture among older adults, whether or not they have diabetes. Furthermore, several studies of people with Type 1 diabetes have demonstrated that lower BMD is associated with neuropathy (nerve damage), retinopathy (an eye disease), and nephropathy (diabetic kidney disease). More research on diabetic complications is needed to better understand their impact on BMD and fracture risk.
Ensuring bone health
It is critical for people at high risk for osteoporosis to get screened for it so that fractures can be prevented. The major factors that increase the risk of osteoporosis are the following:
- Older age
- Female sex (especially at the time of or after menopause)
- History of fractures as an adult
- History of osteoporosis or fractures in a parent or sibling
- Low body weight (less than about 127 pounds)
Additional factors that may increase the risk of osteoporosis include the following:
- Low calcium or vitamin D intake, especially lifelong
- High alcohol intake (more than two drinks per day)
- Lack of exercise
- Estrogen deficiency in women, especially at an early age
- Some medicines for thyroid conditions
- Use of corticosteroids or immunosuppressive drugs (for asthma, arthritis, cancer, or transplant surgery)
- A variety of other medical conditions including chronic intestinal disorders, nutritional disorders, endocrine disorders, stroke, kidney failure, and organ transplantation