Our bones become dangerously weak with advancing age. A lot of this stems from a growing failure of maintenance processes and an imbalance in the bone remodeling that constantly takes place - too much bone removal, and not enough creation. In addition, however, rising levels of the sugary metabolic wastes known as advanced glycation endproducts (AGEs) are also thought to play a role in weakening tissue structures like bone. There are many different types of AGE and not all are relevant to this type of dysfunction: some are short-lived and usually cleared out by the body, and thus their presence indicates a failure in clearance mechanisms or some form of metabolic dysfunction such as diabetes, while others are long-lived and hard for the body to break down, and these build up steadily over time. There is a wide range of current capabilities for measuring and manipulating AGEs: the basic toolkit for working with the most important long-lived human AGE glucosepane is only now being developed, for example.
Here researchers demonstrate an association between one common species of AGE and increasing bone frailty independent of the loss of bone density. Because of the points noted above this is a case of measuring what you can measure with the data to hand - it would be interesting to see this same data with glucosepane levels, as the measured form of AGE may be just a marker rather than a measure of the agent of harm:
Advanced glycation end products (AGE) in bone tissue are associated with impaired biomechanical properties and increased fracture risk. Here we examine whether serum levels of the AGE carboxy-methyl-lysine (CML) are associated with risk of hip fracture. We followed 3373 participants from the Cardiovascular Health Study (age 78 years; range, 68-102 years; 39.8% male) for a median of 9.22 years. Rates of incident hip fracture were calculated by quartiles of baseline CML levels, and hazard ratios were adjusted for covariates associated with hip fracture risk. A subcohort of 1315 participants had bone mineral density (BMD) measurement.
There were 348 hip fractures during follow-up, with incidence rates of hip fracture by CML quartiles of 0.94, 1.34, 1.18, and 1.69 per 100 participant-years. The unadjusted hazard ratio of hip fracture increased with each 1 standard deviation increase (189 ng/mL) of CML level (hazard ratio 1.27). Sequential adjustment for age, gender, race/ethnicity, body mass index (BMI), smoking, alcohol consumption, prevalent coronary heart disease (CHD), energy expenditure, and estimated glomerular filtration rate (based on cystatin C), moderately attenuated the hazard ratio for fracture to 1.17. In the cohort with BMD testing, total hip BMD was not significantly associated with CML levels. We conclude that increasing levels of CML are associated with hip fracture risk in older adults, independent of hip BMD. These results implicate AGE in the pathogenesis of hip fractures.