AGE Burden and Response to Antiresorptive Therapy in Osteoporosis

Association of Advanced Glycation End-Product Burden With Response to Antiresorptive Therapy and Residual Fracture Risk in Osteoporosis: A Prospective Cohort Study

Osteoporosis is a common condition that increases the risk of bone fractures. Although antiresorptive treatments such as bisphosphonates and denosumab are effective in increasing bone mineral density, some patients continue to experience fractures despite treatment.

Advanced glycation end-products (AGEs) accumulate in the body over time and can negatively affect bone quality by altering collagen structure and increasing inflammation. The role of AGE burden in predicting response to osteoporosis treatment has not been fully established.

This prospective cohort study aims to evaluate whether baseline AGE burden, measured non-invasively using skin autofluorescence, is associated with treatment response in patients receiving antiresorptive therapy for osteoporosis. Changes in bone mineral density, bone turnover markers, and fracture outcomes will be analyzed in relation to baseline AGE levels. The results of this study may help identify patients at risk for reduced treatment response and residual fracture risk.

Inclusion Criteria:

• Age ≥ 50 years
• Diagnosis of osteoporosis based on dual-energy X-ray absorptiometry (DXA) criteria (T-score ≤ -2.5 at the lumbar spine, total hip, or femoral neck) or presence of a prior fragility fracture
• Planned initiation of antiresorptive therapy (denosumab or bisphosphonate) as part of routine clinical care
• Ability to undergo DXA measurements at baseline and during follow-up
• Ability and willingness to provide written informed consent

Exclusion Criteria:

• Diagnosis of diabetes mellitus (type 1 or type 2)
• Chronic kidney disease with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m²
• Active malignancy or history of malignancy within the past 5 years
• Secondary causes of osteoporosis (including hyperparathyroidism, hyperthyroidism, Cushing's syndrome, malabsorption syndromes, or chronic liver disease)
• Use of medications known to significantly affect bone metabolism other than antiresorptive therapy (e.g., long-term systemic glucocorticoids, anabolic osteoporosis agents)
• Prior treatment with denosumab or bisphosphonates within the last 12 months
• Inflammatory rheumatic diseases or chronic inflammatory conditions that may affect bone metabolism
• Pregnancy or breastfeeding
• Inability to comply with study procedures or follow-up visits