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CHICAGO -- Diabetes can add an extra layer of challenge for clinicians managing patients with osteoporosis.

It's widely known to endocrinologists that diabetes -- both type 1 and type 2 -- can affect bone health and put patients at a higher risk for fracture.

"This increased fracture risk has been demonstrated in large studies including the Women's Health Initiative," Maria Skamagas, MD, of the Icahn School of Medicine at Mount Sinai in New York City, told 番茄社区.

Current research pegs the risk of fracture for people with type 1 diabetes as much as five to 10 times higher than for patients without diabetes, while the risk for those with type 2 is not quite as steep -- around two times as high -- commented Rajesh Jain, MD, of Temple University Hospital in Philadelphia.

"The difficult thing about patients with type 2 diabetes is that although they have increased risk of fracture, they often have greater bone density than those without type 2 diabetes," Jain told 番茄社区. "Instead, it is thought that patients with type 2 diabetes have impaired bone quality, which is difficult to measure with routine tools. Many groups are actively researching what the best tools might be to predict fracture risk in those with diabetes."

"Those who are overweight or obese tend to have higher [bone mineral density (BMD)] than those with normal [body mass index (BMI)], but when the BMI is accounted for, there is still increased BMD in type 2 diabetes," Skamagas added.

The mechanisms behind this elevated risk, which tends to be greater in patients who have had diabetes for a longer duration, range from low bone turnover linked to the effects of insulin mediated through insulin-like growth factor (IGF)-1 receptors in the bone, defects in cortical bone, as well as accumulation of advanced glycation end products in the bone, she explained.

Specifically for people with type 2 diabetes, other factors that can increase a patient's risk for fracture include poor glycemic control, insulin therapy, and episodes of hypoglycemia.

"In addition, thiazolidinediones (TZDs) have been shown to increase fracture risk in women and possibly in men. There is some evidence that the [sodium-glucose co-transporter 2 (SGLT2)] inhibitors also increase fracture risk," Ann Schwartz, PhD, MPH, of the University of California, San Francisco, told 番茄社区, adding that the current guidelines of the American Diabetes Association (AGA) recommend that TZDs, such as pioglitazone, and SGLT2's, such as canagliflozin, should be avoided in patients with type 2 diabetes at a high risk for fracture.

Skamagas noted when selecting diabetes medications, pioglitazone is a potent oral therapy with high durability over time, but it is associated with increased fracture risk in women, so these may be avoided in women at high risk of fracture for whom there is no alternative medication.

Although the "optimal" prevention strategies to avoid osteoporosis in people with diabetes is not yet known, according to Jain, other preventative strategies for avoiding osteoporosis in people with type 2 diabetes should be similar to those for people without diabetes. This includes attention to good nutrition, and particularly calcium and vitamin D, and weight-bearing physical activity, Schwartz recommended.

As for patients with type 1 diabetes, those diagnosed before age 30 will most likely fail to achieve peak bone mass, in part due to lower insulin and IGF-1 levels resulting in less stimulation of IGF-1 receptions in bone cells, leading to a reduction in bone formation.

"Lower insulin and IGF-1 levels result in less stimulation of IGF-1 receptors in bone cells and reduced bone formation," Skamagas said. "In addition, an individual with type 1 diabetes and fractures should be evaluated for coexisting celiac disease, an autoimmune condition that causes gluten intolerance and malabsorption of calcium, vitamin D, and macro-nutrients like protein. Concomitant eating disorders -- ie., anorexia nervosa -- in young people with type 1 diabetes may result in protein and calcium deprivation and low body weight, low sex steroids (estrogen and testosterone), severe deficit in peak bone mass, and increased fracture risk."

However, people with prediabetes are not thought to have this same increased fracture risk, although high insulin levels in these patients may stimulate IGF-1 receptors and enhance osteoblast functioning and should therefore be monitored closely, she warned.

Identifying those at a higher fracture risk can be of a particular challenge for clinicians treating patients with diabetes.

Jain pointed out the current ADA recommendations say that providers should assess fracture history and risk factors, and then recommend measurement of bone density if appropriate for a patient's age and sex.

"Our standard tools for assessing risk are BMD T-score and algorithms such as FRAX [a diagnostic tool used to evaluate the 10-year probability of bone fracture risk]," said Schwartz. "Both of these approaches can distinguish those with high and low fracture risk among diabetic patients, but tend to underestimate the risk. For example, the risk of hip fracture for a diabetic patient with a BMD T-score of -2.0 is similar to the risk for a non-diabetic patient with a T-score of -2.5. FRAX does not currently take diabetes into account. To roughly adjust FRAX for the presence of diabetes, clinicians can enter a BMD T-score that is 0.5 units lower than the observed T-score."

In regards to recommended treatments for patients with diabetes and osteoporosis, pharmacological therapy should be considered, Schwartz suggested. "Separate guidelines are not available for those with diabetes. Evidence is limited, but bisphosphonates, the current first-line therapy, appear to improve bone density and reduce fracture risk in diabetic as well as non-diabetic patients."

However, other comorbidities that may be present in a patient with osteoporosis and diabetes, such as the presence of renal disease, may dictate the course of the treatment for that patient.

"Both bisphosphonates (alendronate, risedronate), which are the first-line medication, and raloxifene, have been demonstrated to improve BMD and reduce fracture risk in both diabetics and non-diabetics," Skamagas said. "The bisphosphonates require creatinine clearance greater than 30-35 mL/min. The presence of advanced renal disease and secondary hyperparathyroidism would change the focus to managing phosphorus, vitamin D, and [parathyroid hormone].

"The burden of medications and glucose monitoring faced by someone with diabetes, especially with type 1 diabetes, may make the individual less inclined to add more medications to an already extensive regimen," Skamagas continued. "One may be more aggressive in recommending bone medications if there is a history of fragility fracture after age 50."

She said that beyond pharmacologic treatments, it is critical for providers to help patients mitigate risk factors that could contribute to falling. Some ways to do this, she said, include the following:

• Safely promoting muscle strength/flexibility (for example, walking, tai chi, aquatic exercise)
• Reduction of sedative medications, excess alcohol use
• Managing blood pressure to avoid orthostasis, dizziness
• Managing visual impairment (for example, wearing glasses, having a well-lit home)
• Managing neurologic impairment
• Wearing proper footwear
• Using assistive devices when needed (for example, a cane, a walker, a seat/grab bar in the shower)

Other treatment recommendations for patients with osteoporosis, which extends also to patients with diabetes, include having 1,000 to 1,200 mg per day of calcium from diet or supplements as needed and 600 to 800 units of vitamin D per day for a goal of vitamin D25OH above 30 ng/mL, and staying active with 30 to 40 minutes of weight-bearing exercise about 3 or 4 times a week.

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