Severe loss of body height is often a consequence of osteoporotic vertebral fractures. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) are cytokines essential for the regulation of bone resorption. The aim of this study was to assess the relationship between the OPG/RANKL system and height loss. A total of 4,435 inhabitants from the municipality of Tromsø, Norway (2,169 men and 2,266 women) were followed for 6 years. Baseline measurements included height, weight, bone mineral density, OPG, RANKL, serum parathyroid hormone and information about lifestyle, prevalent diseases and use of medication. Height was measured again at follow-up, and the loss of height was categorized into 4 groups: ≤1, 1.1-2, 2.1-3, >3 cm. We found increasing height loss with increasing baseline OPG levels in both men and women (P trend = 0.02 and 0.001, respectively), after adjustments for age and other confounders. However, when the women were stratified according to menopausal status and use of hormone replacement therapy (HRT), a significant relationship was present only among postmenopausal women not using HRT (P trend = 0.02). No relations between OPG and height loss were found in post-menopausal HRT-users and premenopausal women (P trend ≥0.39). We conclude that height loss is positively associated with OPG in men and in postmenopausal women not using HRT. No relationship was found between RANKL and height loss.