With Stavroula Paschou, MD, PhD, and Dorothy Fink, MD
As the burden of diabetes continues to increase, so does the risk of osteoporosis.1 In patients with type 2 diabetes (T2D), the risk of osteoporosis is twice that of the general population, and the challenges of both conditions only increase with age.1,2
Although there are many studies and guidelines that focus on treatment for T2D as well as osteoporosis as distinct conditions, their co-existence presents diagnostic and therapeutic considerations that have, until now, not been addressed simultaneously.
To provide a more targeted approach to the co-management of T2D and osteoporosis, a team of researchers examined the effect that diabetes medications may have on bone metabolism and the impact that osteoporosis treatments may have on glycemic control, and published their recommendations to encourage more coordinated care in the Journal of Clinical Endocrinology & Metabolism.3
Dr. Paschou reviewed the recommendations derived from the systematic review3 with EndocrineWeb, for the benefit of endocrinologists and others who care for those with diabetes and osteoporosis to enhance patient care going forward.
"A Mediterranean-style diet and physical exercise remain very important for the prevention and treatment of both entities," Dr. Paschou said, "and these lifestyle behaviors will serve patients well the sooner they are begun. However, most patients will require pharmacological intervention, at some point, due to the usual conditions that arise in people who have diabetes for many years.”
As for effects that osteoporosis medications may have on glucose metabolism, no evidence of detrimental outcomes was found, Dr. Paschou said, whereas a possible beneficial effect has been seen with the use of bisphosphonates.5
Highlights of the co-management guidelines derived from the systemic review follow:3
"Metformin, sulfonylureas, dipeptidyl peptidase 4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP1-RA) should be the preferred treatment in these patients [due to lower fracture risk] while strict targets should be avoided for the fear of hypoglycemia, falls and fractures," Dr. Paschou said, especially in older adults who are at greatest risk for fracture.
"Thiazolidinediones and canagliflozin should be avoided due to the increased fracture risk," Dr. Paschou said, "Within a few years of thiazolidinediones entering routine clinical use in the treatment of T2D, signals emerged suggesting a concern with reduced bone density and increased fracture risk."
Given the greater risk of falls associated with low blood sugar, "insulin should be used with caution and careful measures to avoid hypoglycemia," said Dr. Paschou.
While no randomized controlled trial has looked at the effect of insulin treatment on bone health, ''it has been almost consistently shown that patients who are treated with insulin present [with] an increased prevalence of fractures." Dr. Paschou said. However, if a patient with T2D is hospitalized with a bone fracture, insulin therapy remains the preferred method for achieving better glycemic control.
"Regarding bone health, it has been shown that canagliflozin exerts negative effects on bone mineral density (BMD), bone resorption, and fracture risk at the hip," said Dr. Paschou.
On the other hand, dapagliflozin, empagliflozin, and dapagliflozin have not been shown, in general, to exert significant changes in BMD, bone markers or fracture risk, therefore seem to present a rather neutral effect on bone metabolism, Dr. Paschou said.
However, the concerns [about increased fracture risk] raised by studies with canagliflozin,6,7 inevitably affect the whole class," she said, therefore, "further studies are needed to elucidate the mechanisms of bone loss and the real safety profile among these newly used medications, regarding the overall benefits to patients."
“Managing coexisting diabetes and osteoporosis well is a necessary challenge,” said Dorothy Fink, MD, an endocrinologist and attending assistant physician at the Hospital for Special Surgery in New York City.
“T2D is being diagnosed at a much earlier age," said Dr. Fink, “so there is a need to both carefully consider the diabetes medications prescribed and their long-term effects on bone health, especially in younger patients.”
"In general, I would say endocrinologists [and others who care for those with diabetes] should have bone health on their minds," she told EndocrineWeb, "But the complications of diabetes are endless, so it's not always the first thing to be considered, understandably."
“That makes this review and guide timely and necessary,”3 Dr. Fink said, as more research will help to spell out the best way forward to co-manage diabetes and preserve bone health in our patients.
"As a first step, adding another medication to a patient's regimen when they haven't fully adopted a new outlook on managing their diabetes with diet is something we need to challenge patients with," Dr. Fink said.
Dr. Fink has found that ''checking blood sugar to figure out how food affects [patients’ blood sugar] can really help them to make constructive changes." For example, a patient may find he has a blood sugar of 200 the day after eating Chinese food, but not after a meal that includes fish and vegetables. That's a clear message about how paying attention to lifestyle can help, she said.
The emphasis on the use of metformin is also important, said Dr. Fink, "If a patient doesn't respond sufficiently, trying metformin extended release would be a good next step."
"Sulfonylureas can cause weight gain," she said, “something no patient welcomes, and should, therefore, be avoided unless all other options have been considered.”
Another drug that Dr. Fink often prescribes with good results is acarbose, which the report does not mention because it is rarely used in Europe and it was not in use at the time the ADA/EASE Guidelines were released.8
Cardiovascular risk adds another layer to the treatment conundrum of patients with T2D. “Patients gain cardiovascular benefits when taking SGLT2 inhibitors, but the cardiovascular benefit may be at the expense of bone health.”6,9
The authors had no financial conflicts to report.