Osteoporosis, Controversial Fractures, and Numerous Bone Markers

Aging and lifestyle-related metabolic imbalances such as hyperglycemia, hyperlipidemia and oxidative stress cause the accumulation of advanced glycation end products (AGEs), including pentosidine (PEN, crosslinked type) and carboxymethyllysine (CML, uncrosslinked type)). Osteoporosis is a common skeletal metabolic disease characterized by decreased bone mineral density (BMD) or bone strength that increases the risk of fractures.

The association of PEN and CML with osteoporotic fractures has been reported to date, and it is believed that the accumulation of AGEs in bone tissue contributes to bone vulnerability via the deterioration of bone matrix proteins, particularly collagen. However, the exact mechanisms of PEN and CML in fracture occurrence are unclear and remain controversial, while studies have not been conducted to find out why CML is associated with fractures. There are no reports examining the effects of PEN and CML on bone metabolism, BMD and fractures in the same patients.

Accordingly, a team of doctors from the Department of Orthopedic Surgery at Shinshu University School of Medicine et al. examined urinary PEN and serum CML levels to assess and compare the effects of these AGEs on bone status and prevalent osteoporotic fractures in a cohort of postmenopausal women.

The group found that both PEN and CML were significantly associated with the predominant vertebral fracture in postmenopausal women. The mechanism of PEN could be independent of the lumbar BMD, while that of CML could be dependent on the BMD. It appears that PEN, a cross-linked type of AGE, is independently associated with the occurrence of breakage via deterioration of the collagen network, resulting in degradation of bone quality without affecting BMD. On the other hand, CML as a non-networked type of AGE could have contributed to the occurrence of fractures through decreased BMD. Both AGEs therefore appear to influence bone status and health, albeit possibly through different mechanisms.

The study’s correspondent author, Associate Professor Yukio Nakamura, stated that this study looked at the effects of PEN and CML on a range of markers, BMD and fractures related to bone turnover in the same postmenopausal outpatients who set up a facility Attended primary care, and this proved possible various mechanisms of these AGEs for the occurrence of fractures. Since this investigation was only a cross-sectional study, the team could not find a causal relationship between AGEs and osteoporotic fractures.

Therefore, the pathophysiological relevance of AGEs in fractures requires confirmation by a prospective longitudinal study design with the general population, e.g. B. Participants from shared apartments. Together with the laboratory experiments, we would like to uncover the epidemiological and mechanistic connections between AGEs and fractures.

Ultimately, the team hopes to provide an effective intervention for the accumulation of AGEs in bone tissue, which will lead to the maintenance of bone health in the elderly.


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