The Impact of Diabetes on Bone Health

By Subbulaxmi Trikudanathan, MD

Diabetes care revolves around controlling blood sugar (glucose) to reduce what we recognize as diabetes complications – those relating to vision, to nerve function, to kidney function and to the vessels of the heart, vessels leading to the brain, and the vessels in the legs. What is not so well recognized is that there is also an issue of bone health when most people think of possible complications of diabetes.

Osteoporosis is a condition in which there is generalized thinning and weakening of your bones, which puts you at risk of a bone fracture. Osteoporosis is very common, affecting nearly 10 million Americans. Among all Caucasian women, one out of every two have a risk of having an osteoporosis-associated fracture in their lifetime. It doesn’t help that as we all get older, bone health plays a larger and larger role for everyone, even more so if you have also been diagnosed with diabetes.

Diabetes adds to an increased risk of fractures. And having diabetes can delay fracture healing if fracture occurs, a double hit. But how does diabetes affect the quality of bone and increase the risk of fracture? Is it just diabetes itself, or other complications of diabetes such as neuropathy (nerve damage)? Or is it the medications that are used to control blood sugars? Let’s look at the evidence.

What is the link between bone density and diabetes?

Bone mineral density (BMD) measures the calcium content of the bone, predicting bone strength and fracture risk. The lower the bone density, the higher the risk of fracture. BMD is measured by a special scan called dual-energy X-ray absorptiometry (DXA). BMD as measured by DXA is decreased in Type 1 diabetes (T1D, the diabetes in which your pancreas does not make insulin), but may be actually normal or even increased in Type 2 diabetes (T2D, the diabetes in which insulin present does not function as it should, plus a loss of production of insulin over time).

There is a three-fold increased risk of hip fracture in patients with T1D. Both a decrease in BMD and bone quality contributes to this higher risk. To add to the confusion, if you have T2D, you have a higher risk of fracture, especially if you are older, despite a normal or increased BMD. Studies suggest an increase of fracture risk at multiple skeletal sites, including shoulder, foot, ankle and spines in women with T2D. Also, with longer duration of Type 2 diabetes, you additionally have between a 40 to 70 percent increased risk of hip fracture, regardless of age, body size (short or tall, lean or overweight) and BMD. These findings suggest that the bone fragility is caused by changes of the bone quality and microarchitecture rather than having just less dense bones.

Why is bone affected in diabetes?

High blood glucose decreases the formation of osteoblasts, also known as the body’s bone-forming cells. Chronically high blood glucose leads to the accumulation of certain compounds (named advanced glycation end-products) in the bone structure that affects the bone-forming cells. There is a balance between bone formation and bone breakdown in our skeleton. This dynamic process is called bone remodeling. In patients with diabetes, bone remodeling is disturbed by the accumulation of advanced glycated end-products, leading to deterioration in the bone quality. Higher homocysteine levels (an amino acid and breakdown product of protein metabolism) seen in diabetes may also be involved in decreased bone formation and remodeling. Lack of insulin and insulin-like growth factor affect bone mass and strength in patients with diabetes. So, a number of interferences with normal bone’s constant restructuring are present when you have diabetes, and especially if your blood sugar is not controlled.

What are the reasons for higher fracture risk if you have diabetes?

Diabetic kidney disease affects bone metabolism as well as the bone microarchitecture. And diabetes reduces muscle mass and muscle quality and strength, adding to balance issues. Poor balance leads to an increased likelihood of falling. Apart from changes in bone microarchitecture and quality, several other factors play a role in increasing the risk of fractures with diabetes. A complication of diabetes affecting the nerves – peripheral neuropathy – can lead to poor balance and consequently increases the risk of falling. Neuropathy can also cause bone loss with increased fracture risk, particularly in the feet and ankles. Reduced vision from cataracts or diabetic retinopathy (eye disease) may also contribute to an increased frequency of falls.

How do blood sugar-lowering or antidiabetes medications affect the bone?

Certain diabetes medications, such as rosiglitazone and pioglitazone, which belong to a class of drugs called thiazoledinediones, can steer the development of stem cells (what are also called precursor cells) into fat cells, rather than boneforming cells. Several studies have shown reduced bone density in the spine and hips in women treated with thiazoledinediones. Given this, some experts recommend these drugs should not be used by postmenopausal women who also have diabetes.

One of the newer antidiabetes medications, sodiumglucose cotransporter-2 (SGLT-2) inhibitors, particularly canagliflozin, have been reported to have adverse effects on bone health. A recent study reported increased risk of fracture starting from 3 months of treatment with canagliflozin. This adverse effect was not reported with empagliflozin, another medication in the same class. So it remains unclear if it is a drug class effect or unique to canagliflozin. The skeletal effect of SGLT2 inhibitors is thought to work through increased phosphate and parathyroid hormone (a hormone closely responsible for maintaining calcium and phosphorus balance in our body) in the blood. However, further studies are needed to clarify the effects of SGLT2 inhibitors on bone.

Other antidiabetic medications such as metformin, sulfonylurea and incretin-like drugs do not cause adverse skeletal effects. Some studies indicate that metformin may actually be protective to the bones. There is no data that insulin treatment by itself can affect the bone but, curiously, there are more fractures seen in insulin-treated individuals. This may be due to longer duration of diabetes, the presence of diabetes complications and hypoglycemic events leading to increased risk of falls. These associations need more intensive investigation.

What tests can help me get more information about my bone health?

Evaluation of bone health starts with a thorough history regarding the duration of diagnosed diabetes, the presence of any diabetic complications, and what diabetes medications have been or are currently being used. Age, sex, body weight, use of drugs that contain steroids (such as prednisone), smoking, alcohol use, menopausal status, rheumatoid arthritis, prior history of fracture and family history of osteoporosis are all used in the risk factor assessment for bone health or fracture risk. Currently there are no specific screening guidelines for individuals with diabetes. The National Osteoporosis Foundation (NOF) recommends BMD testing with DXA scan in all women aged 65 years and older and men aged 70 years or older. In women and men aged 50-65 years, DXA scan can be performed earlier based on the individual’s risk factor profile.

Fracture risk assessment tool (FRAX), a computer-based program, is another valuable tool for evaluating future risk for fractures and making treatment decisions. FRAX can predict the probability of future osteoporotic fractures over the next 10 years based on BMD and other risk factors. However, as discussed earlier, individuals with type 2 diabetes may have normal BMD, which underestimates risk for osteoporoticrelated fractures. The option of adding diabetes in the FRAX tool programming has been considered, but requires more data from different population groups worldwide.

How and when is osteoporosis treated?

Adopting a healthy lifestyle consisting of exercise, and taking calcium and vitamin D, form the cornerstone of any treatment plan. The American Association of Clinical Endocrinologists (AACE ) recommends women 50 years or older take 1,200 milligrams of calcium daily. This can come from diet (which is often preferred), or calcium supplements if dietary intake is insufficient. For men, the recommendation is 1,000 milligrams daily, until age 71 or older, then 1,200 milligrams daily is recommended.

Many calcium supplements are commercially available. Calcium carbonate is generally the least expensive and requires the smallest number of tablets due to a generous calcium content (40 percent). However, calcium carbonate may cause more gastrointestinal (GI) complaints (e.g., constipation and bloating) than calcium citrate. In addition, it requires gastric acid for absorption and is best absorbed when taken with meals. Calcium citrate is often more expensive than calcium carbonate and requires more tablets to achieve the desired dose due to a lower calcium content (21 percent), but its absorption is not dependent on gastric acid, and it may be less likely to cause GI complaints. In addition to tablets, which can be large and difficult to swallow, calcium supplements are available as soft chews and gummy preparations. For optimal absorption, calcium supplementation should not exceed 500 to 600 milligrams per dose, regardless of the preparation. The dose should be divided if the intake requires more than 600 milligrams daily.

It is advisable to have a vitamin D level checked before deciding on what is needed for replacement. The dose of vitamin D needed to correct a deficiency varies among individuals. Recent results suggest doses greater than 1,000 IU (International Unit) or even 4,000 IU of vitamin D per day may be needed. Due to the limited amount of food products containing sufficient vitamin D (for example, fresh salmon with up to 1,000 IU and shitake mushrooms with 1,600 IU), AACE recommends vitamin D supplementation to achieve a level of vitamin D equal to or over 30 nanogram/milliliters (ng/ml), but under 50 ng/ml.

Fall prevention also needs to be addressed. AACE recommends the following preventive measures be taken:

  • Anchor rugs
  • Minimize clutter
  • Remove loose wires
  • Use nonskid mats
  • Install handrails in bathrooms, halls and long stairways
  • Light hallways, stairwells and entrances
  • Wear sturdy, low-heeled shoes
  • Hip protectors should be used by patients who are predisposed to falling
  • Keep all items within reach and avoid using stepstool

Whether you will need medication prescribed is something to discuss with your healthcare team. Osteoporosis treatment options for those with diabetes are the same as for those without diabetes. There are several options available that reduce bone breakdown, such as bisphosphonates and denosumab. Other medications that help build bones, such as teriparatide and abaloparitide, are also used in special situations. These osteoporosis treatments do not affect blood glucose control.

Take-home message

Bone quality and bone strength are affected by diabetes. Certain diabetes medications can affect bone health as well. Certain diabetes-related complications can affect the risk of falling, as well as bone density. Discuss with your diabetes treatment team whether your bone health should be examined…and be active in getting the care you need for a healthy, fracture-free future!