OBJECTIVE: To review the literature describing the association of osteoporosis (OP) with scleroderma (SSc). METHODS: A Medline (PubMed) search identified all studies from 1966 to 2004 that investigated the association between OP and SSc. Search terms included "scleroderma," "systemic sclerosis," "osteoporosis, " "bone mineral density," "bone densitometry," and "prevalence." RESULTS: Eight case control studies and 1 retrospective study (comparing OP status to a reference standard) were identified. There is no clear association between bone mineral density (BMD) scores and scleroderma. Two of 4 studies have reported lower BMD scores in SSc, but appear not to have considered possible confounding risk factors. Earlier age of menopause has been reported in 2 of 3 studies, and thus, may be a confounder in some samples of women with SSc. Studies of bone metabolism markers have not provided any consistent explanatory mechanism for increased OP in SSc, and such markers may be unreliable in SSc as these are affected by the altered collagen turnover and fibrosis characteristic of SSc. CONCLUSIONS: It is unknown whether OP is truly increased in SSc or whether this association has been observed in some studies as a result of other confounding risk factors for OP. Clinical heterogeneity of SSc study samples and small sample sizes have contributed to the difficulty in obtaining valid estimates of the risk for the development of OP. There is no strong evidence in the literature for consistently lower BMD scores in SSc, or for altered biomarkers of bone resorption. Earlier menopause, corticosteroid use in some patients, and other factors secondary to SSc (such as malabsorption and inflammation), may be causal factors or may be confounders in studies of OP in SSc.