Diabetes and osteoporosis are complex and connected diseases
Diabetes and osteoporosis, particularly bone loss, have very complex pathophysiologies, according to an expert who gave a rundown of the current state of osteoporosis and diabetes at the recently concluded 6th Asia-Pacific Osteoporosis Meeting (IOF Regionals 2016) in Singapore.
Both diseases are results of multifactorial processes, says Dr Manju Chandran, a senior consultant endocrinologist at the Department of Osteoporosis and Bone Metabolism Unit of the Singapore General Hospital.
Cellular and molecular mechanisms, medication, macro- and micro-architectural changes, and other confounding illnesses may play a role in either of these diseases. “All of these combined can potentiate bone loss as well as fractures and diabetes,” she notes.
As it turns out, diabetes and osteoporosis are somehow linked to each other. “What has been shown is that … the fracture risk is higher for a given [femoral neck] T score and age in diabetics compared to non-diabetics, and this seems to be the pattern in women as well as men,” says Dr Chandran .
Unfortunately, the existing technique—the FRAX method—to predict fracture risk does not take diabetes—specifically type 2 diabetes—into account. Thus, the FRAX method underestimates the risk of fractures in diabetics.
“It looks as if there is a higher fracture risk for a given FRAX score and this, again, seems to be the pattern you see in women and men,” says Dr Chandran.
In light of this finding, several measures have been proposed to more accurately predict fracture risk in diabetics. These include using the Trabecular Bone Score (TBS), adjusting the FRAX score to accommodate diabetes, and using rheumatoid arthritis as a proxy for diabetes, as the trends seemed to be similar, among others.
Using TBS, in particular, seems to be an effective measure. Despite its shortcomings (it can only indirectly validate bone micro-architecture), it can detect abnormal micro-architecture, which may explain the paradox of higher fracture risk despite higher bone mineral densities in patients with type 2 diabetes.
The complexities and interrelatedness of osteoporosis and diabetes complicate things for clinicians. “Bone and glucose metabolism is a two-way street, as we all know,” Dr Chandran says.
This relationship is particularly evident in medication. That is, as several studies have shown, common medications to diabetes impact the severity of osteoporosis. One of these is thiazolinedione (TZD).
As shown in a meta-analysis, Dr Chandran explains that using TZDs as an approach to type 2 diabetes mellitus has been associated with an increased risk of fractures in females irrespective of age and duration of exposure.
On the other hand, metformin, one of the “stalwart” therapies to diabetes have been shown to have no effect or a slightly protective effect on fracture risk. Sulfonylureas, also one of the “stalwart” therapies, have conflicting evidence regarding their effects on fracture risk.
Moreover, while insulin has been shown to up the risk of fractures in diabetics, this has not been established as a definite causative factor since comorbid hypoglycaemia is also known to play a role in this increased risk.
SGLT2 inhibitors, the newest players in the market of anti-diabetic therapies, have also been shown to affect the risk of fractures. Specifically, canagliflozin has been shown to increase incidence of fractures by 30 percent, most of which occur 12 weeks after initiation of the treatment.
Conversely, anti-osteoporosis therapies should also be impacted by diabetes. However, at least drawing from the post-hoc analyses of randomized clinical trials presented by Dr Chandran, there seems to be no difference in the effects of bisphosphonates between diabetics and non-diabetics.
It is important to note, however, that none of these post-hoc analyses presented took fracture risk into consideration, says Dr. Chandran. The conclusions were instead drawn from bone mineral density values and levels of bone turn-over markers.
By the end of her presentation, the question still remains: How do we treat the patients who have both of diabetes and osteoporosis?
“I’m standing here before you and I’m clueless actually. At this point in time, it’s rather a jungle,” Dr Chandran admits.
As an alternative, she offers general measures, such as reducing tobacco consumption, preventing hypoglycaemia, and assimilating adequate amounts of calcium and vitamin D, among others.
Dr Chandran explains that while the studies have been mounting at an impressive pace, the reality is that there is no clear path to treatment given the available data.