Influence of orlistat on bone turnover and body composition

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Abstract
OBJECTIVE: To investigate the influence of the pancreas lipase inhibitor orlistat (OLS) on calcium metabolism, bone turnover, bone mass, bone density and body composition when given for obesity as adjuvant to an energy- and fat-restricted diet. DESIGN: Randomized controlled double-blinded trial of treatment with OLS 120 mg three times daily or placebo for 1 y. SUBJECTS: Thirty obese subjects with a mean body mass index (BMI) of 36.9±3.7 kg/m2 and a mean age of 41±11 y. Sixteen patients were assigned to OLS and 14 to placebo. MEASUREMENTS: Dual energy X-ray absorptiometry (DXA) measurements of bone mineral and body composition included total bone mineral content (TBMC), total bone mineral density (TBMD), lumbar spine BMC and BMD, forearm BMC and BMD, fat mass (FM), fat free-mass (FFM), percentage fat mass (FM%) as well as a DXA estimate of the body weight. Body composition (FM, FFM and FM%) was estimated by total body potassium (TBK). Indices of calcium metabolism and bone turnover included serum values of ionized calcium (Ca++), iPTH (parathyroid hormone), alkaline phosphatase, 25(OH)-vitamin D, 1,25(OH)2 vitamin D and osteocalcin as well as fasting urinary ratios of hydroxyproline/creatinine and Ca/creatinine (fU-OHpr/creat, fUCa/creat). RESULTS: There were no significant differences between OLS and placebo groups as to any of the body composition variables (FFM, FM, FM%) at baseline or after 1 y treatment. Weight loss was of 11.2±7.5 kg in the OLS group and 8.1±7.5 kg in the placebo group (NS). The changes in FM and FM% were significant in both groups determined by DXA as well as by TBK, but the group differences between these changes were not significant. The composition of the weight loss was approximately 80% fat in both groups. FFM only changed significantly by DXA in the OLS group (−1.3 kg), but the difference from the placebo group was not significant. Forearm BMD in both groups, forearm BMC in the OLS group and TBMD in the placebo group fell discretely but significantly, but there were no significant group differences between the OLS and the placebo-treated group. All biochemical variables except s-osteocalcin changed significantly after 1 y in the OLS group, disclosing a pattern of an incipient negative vitamin D balance, a secondary increase in PTH-secretion, and an increase in bone turnover with the emphasis on an increase in resorption parameters (fU-OHpr/creat, fUCa/creat). In the placebo group, only s-25(OH)vitamin D and fU-OHpr/creat changed significantly, but the pattern was also that of a deteriorated vitamin D status and an increase in PTH levels and bone turnover. The only biochemical variable which was significantly different between OLS and placebo groups after one year was the fU-OHpr/creat ratio, which increased from 12.0 to 20.1 in the OLS group but only from 10.9 to 13.2 in the placebo group. CONCLUSION: One year's treatment with OLS induces a lipid malabsorption which enhances a dietary weight loss without any significant deleterious effects on body composition. OLS induces a relative increase in bone turnover in favour of resorption, possibly due to malabsorption of vitamin D and/or calcium. However, no changes in bone mass or density are seen after 1 y of OLS treatment apart from those explained by the weight loss itself. Thus 1 y of OLS treatment seems safe from a ‘bone preserving’ point of view. A vitamin D and calcium supplement should be taken during the treatment.