The mechanical properties of bone tissue are the result of a complex process involving collagen-crystal interactions. The mineral density of the bone tissue is correlated with bone strength, whereas the characteristics of collagen are often associated with the ductility and toughness of the bone. From a clinical perspective, bone mineral density alone does not satisfactorily explain skeletal fragility. However, reliable in vivo markers of collagen quality that can be easily used in clinical practice are not available. Hence, the objective of the present study is to examine the relationship between skin surface morphology and changes in the mechanical properties of the bone. An experimental study was conducted on healthy children (n = 11), children with osteogenesis imperfecta (n = 13), and women over 60 years of age (n = 22). For each patient, the skin characteristic length (SCL) of the forearm skin surface was measured. The SCL quantifies the geometric patterns formed by wrinkles on the skin's surface, both in terms of size and elongation. The greater the SCL, the more deficient was the organic collagen matrix. In addition, the bone volume fraction and mechanical properties of the explanted femoral head were determined for the elderly female group. The mean SCL values of the healthy children group were significantly lower than those of the elderly women and osteogenesis imperfecta groups. For the aged women group, no significant differences were indicated in the elastic mechanical parameters, whereas bone toughness and ductility decreased significantly as the SCL increased. In conclusion, in bone collagen pathology or bone aging, the SCL is significantly impaired. This in vivo skin surface parameter can be a non-invasive tool to improve the estimation of bone matrix quality and to identify subjects at high risk of bone fracture.