Professor Juliet Compston, Emeritus Professor of Bone Medicine at Cambridge Biomedical Campus, discussed the challenges that diabetes and obesity place on the assessment of bone at the Amgen One conference in Melbourne. “We need to know more about what’s going on, but already we can see some adjustments that need to be made when assessing risk of fracture in these patients,” she explained.

There’s more than just weight behind the challenge of obesity and bone health

The prevalence of obesity has increased across the globe in the last 30 years.^1,2 Prof. Compston noted, “with more obesity we’re seeing previously unrecognised fracture patterns and a new-found appreciation for the importance of interactions between fat and bone.”³

Perhaps ‘normal’ isn’t enough when it comes to BMD and obesity

“While bone mineral density (BMD) is higher in the majority of obese postmenopausal women, it could be argued that a higher BMD is still insufficient to provide ‘normal’ bone strength for the increase in biomechanical loading imposed by increased body weight,”⁴ proposed Prof. Compston.

She demonstrated this with results of a study of weight and age-matched patients with and without fractures that confirmed lower BMD T-scores in patients with fractures than those without.⁵ “We hypothesise that trauma plays a major role in fractures in obese patients. These patients typically are at an increased risk of falling, the impact of a fall is greater, there may be reduced protective responses and sarcopenia all playing a role. Whether bone fragility is increased per se in obesity remains to be established. However, we suspect vitamin D deficiency, secondary hyperparathyroidism and immobility may contribute to reduced bone mass and quality,” she explained.

Prof. Compston noted that “obesity appears to have a protective effect on the risk of hip, wrist and pelvis fracture, yet there is an increased risk of fracture compared with non-obese patients for ankle, lower and upper leg fractures and inconsistent evidence for spinal fractures.”⁵

“When we looked at why this might be we found obese patients requiring the use of arms assist to rise from a sitting position, those with two or more falls in the past year and comorbidities such as asthma, emphysema and diabetes had a higher risk for incident fracture than non-obese patients.”⁵

Don’t rush to reduce weight to save bones

So should we look to reduce weight in obese patients? Prof. Compston discussed a number of studies that indicate weight loss can have adverse effects on bone.^6,7 “Perhaps the most recent and interesting data are on the effects of gastric banding, which show weight loss stabilising around 2 years, but risk of fractures continuing to increase. How the gut microbiome, bone marrow fat, calcium absorption, vitamin D and hormones are changing as a result are yet to be investigated,”⁸ she explained.

However, Prof. Compston thinks there is hope; with some evidence suggesting that when diet-induced weight loss is accompanied by exercise regimens, the adverse effects on bone may be attenuated.⁹ “But for now, more work must be done to understand the best way to reduce weight and preserve bone at the same time,” she concluded.

Obesity, diabetes and bone health are intrinsically linked

Prof. Compston told meeting delegates that obesity was also a risk factor for type 2 diabetes mellitus (T2DM).^{1 “}Patients with T2DM have an increased risk in hip fracture despite having a bone mineral density (BMD) that is normal or high. This is interesting because of the protective effect obesity appears to have on hip fracture, suggesting factors specific to T2DM are at play,”^10,11 she said.

Bone turnover in T2DM is reduced and mineralisation increased

Prof. Compston discussed the theory behind bone turnover in T2DM. “Histomorphometric data are sparse in T2DM, but along with biochemical marker studies suggest that bone turnover is reduced and bone formation may be supressed.¹² What is known about T2DM and bone is obesity and altered glucose metabolism (which are somewhat interdependent) have multiple effects on bone health.¹¹ The downstream effects of these are bone fragility and an increased risk of falls, which can lead to fractures.”¹¹

She explained how hyperglycaemia may be one of the mechanisms behind reduced bone turnover and increased mineralisation.¹¹ “Animal studies have shown that hyperglycaemia has direct effects on osteoclasts, osteoblasts and osteocytes. So why the increased BMD? As bone turnover is associated with increased mineralisation, this could be a contributor to the increased BMD seen in T2DM.”¹²

Yet, as Prof. Compston emphasised, the bones of patients with diabetes can be deceptively brittle. “Advanced glycation end-products (AGEs) increase the brittleness and reduce the toughness of bone,¹³ which has been demonstrated in several studies using both serum or urine pentosidine levels and carboxymethyl-lysine.”^14,15

There’s a need to update fracture risk tools

“So where we are at today is a challenge with estimating fracture risk using existing tools for patients with T2DM,” noted Prof. Compston. She explained how FRAX “takes clinical risk factors into account, but not duration of disease, glycaemic control or history of falls. This means we may be underestimating fracture risk.”¹⁶

Prof. Compston noted that a new diabetes model for fracture risk prediction had been developed using the Manitoba BMD registry.¹⁷ The following adjustments attenuated the effect of diabetes:¹⁷

• rheumatoid arthritis input
• making a trabecular bone score adjustment
• reducing the femoral neck T-score input by 0.5 standard deviations
• increasing the age imput by 10 years

However, Prof. Compston noted that no single method was optimal in all settings and it was likely that other factors would need to be taken into consideration.¹⁷

This article was sponsored by Amgen, which has no control over editorial content. The content is entirely independent and based on published studies and experts’ opinions, the views expressed are not necessarily those of Amgen.

References

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