The
effect of obesity on fracture risk is divergent; it demonstrates site-dependency,
the risk being increased for some fractures (humerus, ankle, upper arm) and
decreased for others (hip, pelvis, wrist). The relationship between obesity and
fracture also varies by sex, age, and ethnicity. Risk factors for fracture in
obese individuals appear to be similar to those in non-obese populations,
although patterns of falling and the effects of increased skeletal loading are
particularly important in the obese. Research is needed to determine if, and
how, visceral and intramuscular adipose tissue, and metabolic complications of
obesity (insulin resistance, chronic inflammation, etc.) are causally
associated with bone mineral density (BMD) and fragility fracture risk.
Diabetes is also an independent
risk factor for osteoporosis and fractures, although the mechanism of bone loss
differs in type 1 and type 2 diabetes. In type 1 diabetes, which often has its
onset during the acquisition of peak bone mass, there is a six-fold increase in
fracture risk. The main effect is due to insulin deficiency, which leads to decreased
bone formation, low rates of bone modelling and remodelling, and low bone
density. By contrast, in type 2 diabetes, BMD is often increased, yet fracture
risk is doubled. This is due to reduced bone quality and effects of advanced
glycation end-products (AGEs) on non-enzymatic collagen cross-linking to
increase bone fragility. In animal studies increased
bone levels of one of these AGEs, pentosidine, are associated with reduced bone
strength. Serum pentosidine levels have also been associated with an increased
risk of vertebral fractures in postmenopausal women with diabetes, independent
of BMD.
New
techniques to examine bone quality in type 2 diabetes are: high-resolution pQCT
(which has shown increased cortical porosity); trabecular bone score; and micro-indentation
of tibial bone. In both types of diabetes, complications such as low vision,
diabetic nephropathy, and peripheral and autonomic neuropathy, all increase the
risk for falls and fractures. The class of oral anti-diabetic drugs known as glitazones decrease bone
formation and promote bone loss and osteoporotic fractures in postmenopausal
women. GLP-2 agonists decrease bone resorption and increase
BMD, while DPP-4 inhibitors use is associated with decreased fracture risk and an
increase in bone formation markers. SGLT-2 inhibitor use is associated with an
increase in fracture risk. Dapagliflozin
use does not change BTMs or BMD, but is associated with an increase in fracture
risk in those with moderate CKD. Canagliflozin use is associated with higher
CTX and an increased risk of upper limb fractures.
In
conclusion, diabetes and, to a lesser extent, obesity, are important, but
neglected, risk factors for fractures. BMD is not decreased in type 2 diabetes,
so the diagnosis may only be made after a minimal trauma fractures. Despite
reduced bone remodelling and bone formation being features of bone disease in
diabetes, all anti-osteoporosis drugs seem to be effective.