Evidence implicates leptin in obesity and joint damage; a significant association has been found between baseline leptin levels and increased biomarkers of bone formation (osteocalcin and PINP) over a 2-year period; conversely, higher levels of soluble leptin receptor (sOB-Rb), which reduces leptin activity, were associated with lower osteocalcin levels at 2 years of follow-up [54]. The gene discussed is BGLAP; the disease is obesity due to melanocortin 4 receptor deficiency.