Influence of orlistat on bone turnover and body composition

Abstract

OBJECTIVE:To investigate the in¯uence 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 AE 3.7 kgam 2 and a mean age of 41 AE 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 hydroxyprolineacreatinine and Caacreatinine (fU-OHpracreat, fUCaacreat). RESULTS: There were no signi®cant 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 AE 7.5 kg in the OLS group and 8.1 AE 7.5 kg in the placebo group (NS). The changes in FM and FM% were signi®cant in both groups determined by DXA as well as by TBK, but the group differences between these changes were not signi®cant. The composition of the weight loss was approximately 80% fat in both groups. FFM only changed signi®cantly by DXA in the OLS group (71.3 kg), but the difference from the placebo group was not signi®cant. Forearm BMD in both groups, forearm BMC in the OLS group and TBMD in the placebo group fell discretely but signi®cantly, but there were no signi®cant group differences between the OLS and the placebo-treated group. All biochemical variables except s-osteocalcin changed signi®cantly 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-OHpracreat, fUCaacreat). In the placebo group, only s-25(OH)vitamin D and fUOHpracreat changed signi®cantly, 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 signi®cantly different between OLS and placebo groups after one year was the fU-OHpracreat 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 signi®cant deleterious effects on body composition. OLS induces a relative in...

Effects of obesity treatments on bone mineral density, bone turnover and fracture risk in adults with overweight or obesity

“…The changes in lumbar spine and total body BMD from pre-treatment to 12 months were not significant in either group. Significant weight losses of 11.2 ± 7.5 kg (mean ± SD) and 8.1 ± 7.5 kg were measured in the orlistat and placebo groups, respectively, albeit the difference between groups was not significant in this particular trial [79].…”

“…A single clinical trial suggests that orlistat is not associated with any loss of BMD or bone mineral content (BMC) over and above the effect of placebo and associated weight loss [79]. This 12-month, prospective, randomized, placebo-controlled trial of orlistat treatment (120 mg, 3 times a day) in 30 obese participants with a mean age of 41 ± 11 years, showed that mean forearm BMD decreased significantly by 0.01 g/cm 2 from pre-treatment values to 12 months in the orlistat group, with no difference in treatment effect between the orlistat and placebo groups.…”

Changes in fat-free mass during significant weight loss: a systematic review

“…8,59 Only one study of 16 subjects treated with orlistat met the inclusion criteria. 25 The effects of sibutramine on FFM loss are also understudied, with only two studies including only 27 subjects meeting the inclusion criteria. 34,33 It is of note that the %FFML in both these small studies was higher than could be expected for the associated LCD, raising significant concern about the components of weight loss with this medication.…”

“…In this placebo controlled RCT, orlistat caused a marginal increase in weight loss, but made no change to the proportion of weight loss consisting of FFM compared to a LCD alone (Table 2). 25 Surgically induced weight loss When compared to LAGB, both BPD (Po0.001) and RYGB (P ¼ 0.002) caused greater %FFML. The median (IQR) %FFML was 25.6 (11), 31.3 (12.2) and 17.5 (3.7)% following BPD, RYGB and LAGB, respectively.…”

Overview of paediatric obesity for the paediatric mental health provider

“…A 12-month study of orlistat treatment in adolescents resulted in a decrease in BMi by 0.55 kg/m 2 in the treated group versus BMi gain of 0.31 in the controls (Chanoine et al, 2005). Orlistat therapy may reduce fat soluble vitamin levels (A, D, E, K) due to lipase inhibition and has frequently reported unpleasant side effects including flatus (Gotfredsen et al, 2001). Monitoring of 25-OH vitamin D levels during therapy and supplementation of fat soluble vitamins is recommended.…”