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Influence of orlistat on bone turnover and body composition

International Journal of Obesity volume 25, pages 1154–1160 (2001)Cite this article

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.

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References

  1. Sjøstrøm L, Rissanen A, Andersen T, Boldrin M, Golay A, Koppeschaar HPF, Krempf M . Randomised placebo-controlled trial of OLS for weight loss and prevention of weight regain in obese patients Lancet 1998 352: 167–173.

    Article  Google Scholar 

  2. Dalén N, Halberg D, Lamke B . Bone mass in obese subjects Acta Med Scand 1975 197: 353–355.

    Article  Google Scholar 

  3. Rickers H, Balslev I, Foltved H, Rødbro P . Bone mineral content before and after bypass operation in obese patients Acta Med Scand 1981 209: 203–207.

    Article  CAS  Google Scholar 

  4. Krølner B, Ranløv PJ, Clemmesen T, Nielsen PS . Bone loss after gastroplasty for morbid obesity: side-effect or adaptive response to weight reduction? Lancet 1982 i: 956–957.

    Article  Google Scholar 

  5. Kin K, Kushida K, Yamazaki K, Okamoto S, Inoue T . Bone mineral density of the spine in normal japanese subjects using dual-energy X-ray absorptiometry: effect of obesity and menopausal status Calcif Tissue Int 1991 49: 101–106.

    Article  CAS  Google Scholar 

  6. Lindsay R, Cosman F, Herrington BS, Himmelstein S . Bone mass and body composition in normal women J Bone Min Res 1992 7: 55–63.

    Article  CAS  Google Scholar 

  7. Compston JE, Bhambhani M, Laskey MA, Murphy S, Khaw KT . Body composition and bone mass in post-menopausal women Clin Endocrinol 1992 37: 426–431.

    Article  CAS  Google Scholar 

  8. Compston JE, Laskey MA, Croucher PI, Coxon A, Kreitzman S . Effect of diet-induced weight loss on total bone mass Clin Sci 1992 82: 429–432.

    Article  CAS  Google Scholar 

  9. Hyldstrup L, Andersen T, McNair P, Breum L, Transbøl I . Bone metabolism in obesity: changes related to severe overweight and dietary weight reduction Acta Endocrinol 1993 129: 393–398.

    Article  CAS  Google Scholar 

  10. Rosen CJ, Donahue LR . Parathyroid hormone and osteoporosis Curt Opin Endocrinol Diabetes 1996 3: 532–539.

    Article  CAS  Google Scholar 

  11. Frost HM . Obesity, and bone strength and ‘mass’: a tutorial based on insights from a new paradigm Bone 1997 21: 211–214.

    Article  CAS  Google Scholar 

  12. Jørgensen NR . Cytokines and osteoporosis Ugeskr Læger 1997 160: 24–28.

    PubMed  Google Scholar 

  13. Andersen T, McNair P, Hyldstrup L, Fogh-Andersen N, Nielsen TT, Astrup A, Transbøl I . Secondary hyperparathyroidism of morbid obesity regresses during weight reduction Metabolism 1988 37: 425–428.

    Article  CAS  Google Scholar 

  14. Andersen T, Juhl E, Quaade F . Jejunoileal bypass for obesity—what can we learn from a literature study? Am J Clin Nutr 1980 33: 440–445.

    Article  CAS  Google Scholar 

  15. Danø P, Christiansen C . Calcium absorption and bone mineral content following intestinal shunt operation in obesity Scand J Gastroenterol 1974 9: 775–779.

    PubMed  Google Scholar 

  16. Hey H, Lund B, Sørensen OH, Lund BJ, Christensen MS . Impairment of vitamin D and bone metabolism in patients with bypass operation for obesity Acta Med Scand 1979 624 (Suppl): 73–78.

    CAS  Google Scholar 

  17. Tothill P, Avenell A, Reid DM . Precision and accuracy of measurements of whole-body bone mineral: comparison between Hologic, Lunar and Norland dual-energy x-ray absorptiometers Br J Radiol 1994 67: 1210–1217.

    Article  CAS  Google Scholar 

  18. Tothill R, Avenell A, Love J, Reid DM . Comparisons between Hologic, Lunar and Norland dual-energy x-ray absorptiometers and other techniques used for whole-body soft tissue measurements Eur J Clin Nutr 1994 48: 781–794.

    CAS  PubMed  Google Scholar 

  19. Gotfredsen A, Bæksgaard L, Hilsted J . Body composition analysis by DEXA by using dynamically changing samarium filtration J Appl Physiol 1997 82: 1200–1209.

    Article  CAS  Google Scholar 

  20. Hendel HW, Gotfredsen A, Andersen T, Højgaard L, Hilsted J . Body composition during weight loss in obese patients estimated by dual energy x-ray absorptiometry and by total body potassium Int J Obes Relat Disord 1996 20: 1111–1119.

    CAS  Google Scholar 

  21. Forbes GB, Gallup J, Hursh JB . Estimation of total body fat from potassium-40 content Science 1961 133: 101–102.

    Article  CAS  Google Scholar 

  22. Mosekilde L, Charles P, Lindegreen P . Determinants for serum 1,25-dihydroxycholecalciferol in primary hyperparathyroidism Bone Miner 1989 5: 279–290.

    Article  CAS  Google Scholar 

  23. Lund B, Sorensen OH . Measurement of 25-hydroxyvitamin D in serum and its relation to sunshine, age and vitamin D intake in the Danish population Scand J Clin Lab Invest 1979 39: 23–30.

    Article  CAS  Google Scholar 

  24. Hyldstrup L et al. Presented at the IXth International Conference on Calcium Regulating Hormones and Bone Metabolism Nice 1986.

  25. Bergman I, Loxley R . The determination of hydroxyproline in urine hydrolysates Clin Chim Acta 1970 27: 347–349.

    Article  CAS  Google Scholar 

  26. Bertels H, Bohmer M, Heierli C . Serum creatinine dertimination without protein precipitation Clin Chim Acta 1972 37: 193–197.

    Article  Google Scholar 

  27. Schelkopf GM, Milne DB . Wet microwave digestion of diet and fecal samples for inductively coupled plasma analysis Anal Chem 1988 60: 2060–2062.

    Article  Google Scholar 

  28. Harris SS, Dawson-Hughes B . Weight, body composition, and bone density in postmenopausal women Calcif Tissue Int 1996 59: 428–432.

    Article  CAS  Google Scholar 

  29. Baumgartner RN, Stauber PM, Koehler KM, Romero L, Garry PJ . Associations of fat and muscle masses with bone mineral in elderly men and women Am J Clin Nutr 1996 63: 365–372.

    Article  CAS  Google Scholar 

  30. Khosla S, Atkinson EJ, Riggs BL, Melton JL III . Relationship between body composition and bone mass in women Bone Miner Res 1996 11: 857–863.

    Article  CAS  Google Scholar 

  31. Reid IR, Plank LD, Evans MC . Fat mass is an important determinant of whole body bone density in premenopausal women but not in men J Clin Endocrinol Metabol 1991 75: 779–782.

    Google Scholar 

  32. Douchi T, Oki T, Nakamura S, Ijuin H, Yamamoto S, Nagata Y . The effect of body composition on bone density in pre- and postmenopausal women Maturitas 1997 27: 55–60.

    Article  CAS  Google Scholar 

  33. Compston JE, Vedi S, Gianetta E, Watson G, Civalleri D, Scopinaro N . Bone histomorphometry and vitamin D status after biliopancreatic bypass for obesity Gastroenterology 1984 87: 350–356.

    CAS  PubMed  Google Scholar 

  34. Ramsdale SJ, Bassey EJ . Changes in bone mineral density associated with dietary-induced loss of body mass in young women Clin Sci 1994 87: 343–347.

    Article  CAS  Google Scholar 

  35. Jensen LB, Quaade F, Sørensen OH . Bone loss accompanying voluntary weight loss in obese humans J Bone Min Res 1994 9: 459–463.

    Article  CAS  Google Scholar 

  36. Pritchard JE, Nowson CA, Wark JD . Bone loss accompanying diet-induced or exercise-induced weight loss: a randomised controlled study Int J Obes Relat Metab Disord 1996 20: 513–520.

    CAS  PubMed  Google Scholar 

  37. Andersen RE, Wadden TA, Herzog RJ . Changes in bone mineral content in obese dieting women Metabolism 1997 46: 857–861.

    Article  CAS  Google Scholar 

  38. Van Loan MD, Johnson HL, Barbieri TF . Effect of weight loss on bone mineral content and bone mineral density in obese women Am J Clin Nutr 1998 67: 734–738.

    Article  CAS  Google Scholar 

  39. Compston JE, Vedi S, Ledger JE, Webb A, Gazet J-C, Pilkington TRE . Vitamin D status and bone histomorphometry in gross obesity Am J Clin Nutr 1981 34: 2359–2363.

    Article  CAS  Google Scholar 

  40. Tothill P, Avenell A . Errors in dual-energy x-ray absorptiometry of the lumbar spine owing to fat distribution and soft tissue thickness during weight change Br J Radiol 1994 67: 71–75.

    Article  CAS  Google Scholar 

  41. Tothill P, Hannan WJ, Cowen S, Freeman CP . Anomalies in the measurement of changes in total-body bone mineral by dual-energy x-ray absorptiometry during weight change J Bone Min Res 1997 12: 1908–1921.

    Article  CAS  Google Scholar 

  42. Milliken LA, Going SB, Lohman TG . Effects of variations in regional composition on soft tissue measurements by dual-energy x-ray absorptiometry Int J Obes Relat Metab Disord 1996 20: 677–682.

    CAS  PubMed  Google Scholar 

  43. Madsen OR, Jensen J-EB, Sørensen OH . Validation of a dual energy x-ray absorptiometer: measurement of bone mass and soft tissue composition Eur J Appl Physiol 1997 75: 554–558.

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to The Foundation of Director Madsen and his wife Olga Madsen, The Danish Hospital Foundation for Medical Research, Region of Copenhagen, the Faroe Islands and Greenland, and to Hoffmann-La Roche for financial support. We cordially thank Lena Vind, Britta Skotte Hansen, Susanne Svalling for their skilled technical assistance during body composition measurements; Susanne Munch, Susanne Reimer, Vladimira Cvitanicic for laboratory assistance; and Helle Kanstrup for planning the examination program.

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Authors and Affiliations

  1. Department of Endocrinology, Hvidovre University Hospital, Hvidovre, Denmark

    A Gotfredsen, H Westergren Hendel & T Andersen

  2. Department of Internal Medicine, Amager Hospital, Copenhagen, Denmark

    A Gotfredsen

  3. Department of Clinical Physiology and Nuclear Medicine, Hvidovre University Hospital, Hvidovre, Denmark

    H Westergren Hendel

  4. Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    H Westergren Hendel

  5. Roskilde County Hospital, Roskilde, Denmark

    T Andersen

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Correspondence to A Gotfredsen.

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Gotfredsen, A., Westergren Hendel, H. & Andersen, T. Influence of orlistat on bone turnover and body composition. Int J Obes 25, 1154–1160 (2001). https://doi.org/10.1038/sj.ijo.0801639

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