SAMJ I ARTICLES

In the past, most epidemiological studies that examined Body fat distribution as a the association between obesity and disease considered only total and ignored its distribution. risk factor for osteoporosis Recently it has become apparent that it is not obesity per se, but the regional distribution of adipose tissue, that Renee Blaauw, Eisa C. Albertse, Stephen Hough correlates with many obesity-related morbidities including atherosclerosis, hypertension, hyperlipidaemias and 4 mellitus. -8 Objective. The aim of this study was to compare the body The anatomical distribution of adipose tissue differs fat distribution of patients with osteoporosis (GP) with that between men and women in both normal and obese of an appropriately matched non-GP control group. individuals, suggesting that sex hormones are involved in Design. Case control study. the regulation of adipose tissue metabolism.5--10 Upper body Setting. Department of and Metabolism, (android or waist) obesity, which is typically observed in men, is associated with hyperandrogenism, whereas lower Tygerberg Hospital. body (gynoid or hip) obesity is far more common in women, Participants. A total of 56 patients with histologicatly suggesting an oestrogenic influence.':>-12 Moreover, upper proven idiopathic GP, of whom 39 were women (mean age body obesity has been shown to be associated with 61 ± 11 years) and 17 men (49 ± 15 years), were compared hypercortisolism and classically occurs in patients with with 125 age- and sex-matched non-OP (confirmed by Cushing's syndrome. 13 Since hypogonadism and dual energy X-ray absorptiometry) subjects, 98 women hypercortisolaemia are well-known causes of GP, we questioned whether this disease was also associated with (60 ± 11 years) and 27 men (51 ± 16 years). changes in the regional distribution of adipose tissue. The Outcome measures. Anthropometric data, including aim of this study was therefore to compare the body fat weight, height, skinfold measurements, mid-upper arm, distribution of patients with proven idiopathic GP with that of waist and hip circumferences, as well as elbow breadth. an appropriately matched non-ap control group. Results. The men and women with OP were significantly shorter (P = 0.04 and P = 0.03 respectively) and of lower body mass (P = 0.04 and P = 0.02 respectively) than the Materials and methods control subjects, although their mean body mass indices were comparable. The OP population had significantly Subjects lower skinfold, elbow breadth and ann circumference All the subjects in the ap group had proven idiopathic OP values, although the majority of subjects in both groups on dual-energy X-ray absorptiometry (OEXA), as well as a fe/l within the 15 - 85th percentiles. Despite their lower clinical, radiological, biochemical and histological (quantitative histomorphometry after time-spaced body mass, both the OP women (P = 0.009) and men tetracycline labelling of undecalcified bone biopsies) (P 0.002) had significantly higher waist/hip ratios than = work-up, thereby excluding individuals with (I) secondary corresponding controls. OP and (if) metabolic bone diseases other than OP, e.g. Conclusion. Whatever the underlying pathogenesis, this osteomalacia, hyperparathyroidism. The group consisted of new finding suggests that, should these results be 56 Caucasian subjects, consecutively admitted to our confirmed by larger studies, OP can be added to the list of Endocrine Unit for evaluation of their ap, of whom 17 were men and 39 women. The mean age of the men was 49 diseases associated with a waist fat distribution. (±15) years and that of the women 61 (±11) years. S Atr Med J 1996; 86: t081-1084. The control group consisted of 125 age- and sex-matched Caucasian subjects of whom 27 were men and 98 women, of mean ages 52 (±16) years and 60 (±10) years respectively. Osteoporosis (OP) is an extremely common disorder, The absence of osteopenia in this group was confirmed by characterised by a decrease in bone mineral density (BMO) DEXA that results in an increased propensity to fracture which 1 3 most often involves the spine, hip or wrist. • The Methods pathogenesis and risk factors which predispose to the development of OP, however, remain ill-defined. Bone mass was measured by means of OEXA (Hologic OOR-1000) in all the SUbjects and included the lumbar spine (L1 - L4) and hip. Osteopenia was diagnosed if the BMD was found to be decreased by more than 1.5 standard deviations (SOs) in subjects younger than 40 years, or by Department of Human Nutrition and Endocrinology and Metabolic more than 2.0 SOs in those over 40 years of age, compared Unit, University of Stellenbosch and Tygerberg Hospital, Tygerberg, '4 W. Cape with the BMO of young normal subjects. Anthropometric data were obtained from every subject Renee Blaauw. M. NUTR. and included weight, height, skinfold thickness Stephen Hough. M.D. measurements (triceps, biceps, subscapular, supra-iliac), Nutrinet, Pretoria mid-upper arm circumference, waist and hip circumference, Eisa C. Albertse. PH-D. as well as elbow breadth determinations.

SAMJ Volume 86 No.9 September 1996 1081 The following methods were employed: (I) weight - the had a significantly lower body weight than the control SUbjects were weighed with the minimum of clothes on, to subjects. The GP men (P = 0.04) and women (P = 0.03) were the nearest 0.1 kg;15 Qf) height was measured with a sliding also significantly shorter than controls, although all subjects headpiece to increase the accuracy of the readings, which stili maintained an upright posture. Body mass index (BMI) were taken to the nearest 0.1 cm;'5 (iil) skinfolds were values were, however, comparable. Elbow breadth, an measured with a Harpenden caliper. All measurements were indicator of frame size, was significantly lower in the GP taken to the nearest 0.1 mm on the right side of the body: SUbjects compared with controls, although mean values for biceps - over the midpoint of the biceps muscle, triceps ­ both groups were indicative of a medium frame size. The GP over the triceps muscle, midway between the acromial group had significantly lower skinfold and circumference process of the scapula and the olecranon, subscapular­ values for most of the measurements, although the majority just below the tip of the scapula, at 4S Q to the vertical, of subjects in both 9roups fell within the 15 - 85th supra-iliac - just above the iliac crest on the mid-axillary percentiles. From these data it is clear that both the GP and line;'5 (iv) mid-upper arm circumference was measured at the the control subjects were of normal weight. same point as the triceps skinfold;15 (v) waist circumference was detennined in the erect position, around the waist Table I. Bone mineral density of subjects (gJcm~ (mean (SO)) through a point one-third of the distance between the Women Men xiphoid process and the umbilicus;5 (VI) hip circumference OP Control OP Control was assessed in the erect position, around the hips through a point 4 cm below the sUperior anterior iliac spine.s Every Vertebrae effort was made to ensure that the tape was horizontal at L1 - L4 0.72 (0.10)" 1.11 (0.17) 0.72 (0.13)1 1.15(0.13) the back while waist and hip circumference values were Femoral determined. These measurements were taken without Neck 0.60 (0.09)" 0.88 (0.13) 0.64 (0.12)1 0.95 (0.08) ciothing; (vii) elbow breadth, the greatest breadth across the Warn's trian91e 0.39 (0.11)" 0.71 (0.17) 0.39 (0. 16)T 0.69 (0.10) elbow joint, was measured with a sliding caJiper to the 1 Troch 0.50 (0.10)" 0.76 (0.09) 0.54 (0.08)1 nearest 0.1 cm. & 0.80 (0.08) All measurements were made in triplicate by the same Total 0.64 (0.20)" 1.02(0.13) 0.74 (0.12)t 1.09 (0.06) observer, and the results averaged. • P=O.OOOl. Statistical analysis included the Wilcoxon signed-rank tP = 0.008. test, the Spearman correlation coefficient and the Cochran­ Mantel-Haenszel test to determine odds ratios and to obtain The mean waist/hip ratio (WHR) for both control and 95% confidence intervals (95% Cls)." osteoporotic men was nonmal (below 1.0). The WHR for control women of 0.81 (0.05) marginally exceeded the accepted upper limit of 0.80, whereas osteoporotic women had a mean WHR of 0.87 (0.1). In fact, both the osteoporotic Results men (P = 0.002) and women (P = 0.0009) had significantly The BMD of the lumbar spine and various hip areas of both higher WHRs than their corresponding controls (Table 11). the men and the women with OP was significantly lower The odds ratio that a man with a waist fat distribution had than in the comesponding controis (Table I). GP was 8 times higher than that of a man with a hip fat Table 11 lists the anthropometric data of all the subjects. distribution (95% Cl: 1.037 - 61.731), whereas for women rt Both the men (P =0.04) and the women (P =0.02) with GP was 1.6 times higher (95% Cl: 0.751 - 3.588).

Table 11. Anthropometric data on subjects (mean ISOI) Women Men Measurements GP Control P-vaJue OP Control P-vaJue

Body mass (1

1082 Volume 86 No. 9 Septtmber 1996 SAMJ SAMJ

ARTICLES

Discussion and conclusions circulating levels of the anti-resorptive hormone, calcitonin, and protection against parathyroid hormone-mediated bone The relationship between body mass and BMD is well resorption.1-3 Recently, however, oestrogen receptors have established, and a low body mass is classically regarded as been noted in human bone cells.:N Hypogonadism is also a a risk factor for the development of Op'1-3·1s.-20 80th weight well-known cause of osteoporosis in men, and androgens and adiposity could affect BMD in a number of ways. In have potent anabolic effects on skeletal tissue. 40 heavy sUbjects, weight imparts a load factor on weight­ We acknowledge that vertebral compression fractures can bearing bones, resulting in the stimulation of osteoblastic result in decreased height and a change in posture. bone formation. 21 In postmenopausal women, adipose tissue However, even though the osteoporotic subjects were serves as the site of peripheral conversion of significantly shorter than the controls, no posture changes androstenedione to metabolically more active oestrogens, resulting from clinical kyphosis, which might give rise to a known to inhibit bone resorption.20-23 Adiposity cannot, subsequent relatively larger abdominal circumference, were however, be regarded as a homogeneous disorder anymore, observed in this group. We do not believe, therefore, that the and the clinical significance of regional fat distribution is findings are in any way influenced by anatomical posture now well established. changes caused by kyphosis. Because a significant correlation exists between the intra­ Finally, we should take cognisance of the fact that regional abdominal/subcutaneous fat ratio and the WHR, the latter fat distribution, like GP, also has significant genetic has become a useful indirect measure of visceral adiposity determinants.J5 In this regard, the recent observation that and correlates well with many obesity-related morbidities relative truncal adiposity is influenced by a major locus and regardless of whether the BMI is high or IOW,l3,24 polygenic inheritance is of interest.41 Speculation on the A number of metabolic abnormalities have been shown to pathophysiological basis of the observed association be associated with upper body (android) obesity; many of between osteoporosis and regional fat distribution is these may have potentially deleterious effects on skeletal therefore not difficult - further studies are needed, however, integrity. An upper body fat distribution is associated with before the findings of the present study can be placed in increased circulating glucocorticoid levels and Bjorntorp has their proper perspective. hypothesised that it is primarily a maladaptive hypothalamic response to various environmental stressors that results in The authors would like to thank Or C. J. Lombard and Mrs R. increased activity along the corticotrophin (ACTH)-cortisol Laubscher (Institute for Biostatistics, Medical Research Council, axis in these subjects,25 An android profile of fat deposition Tygerberg) for statistical advice. is well established in patients with Cushing's syndrome and it has been suggested that the influence of high cortisol REFERENCES levels on abdominal fat cells could be due to the high 1. Riggs Bl. Melton CJ. The prevention and treatment of osteoporosis. N £ngl J 2E Med 1992; 327: 620-627, .27 density of glucocorticoid receptors in this depot_ Since 2. Dempster DW, Undsay R. Pathogenesis 01 osteoporosis. Lancer 1993; 341: 797­ glucocorticoid excess is known to inhibit bone formation 805. 3. Christiansen C, Riis BJ. Is it possible to predict a fast bone loser just alter the directly,<'ll.2S enhance parathyroid hormone-mediated bone ? In: Peck WA, ed. Bone and Mineral Research. Amsterdam: Elsevier resorption,29 impair renal vitamin 0 hydroxylation and Science Publishers, 1989: 317-332. 4. Hartt AJ, Aupley DC, Aimm AA. The association of girth measurements with intestinal calcium absorption,2.29 and decrease circulating disease in 32 856 women. Am J £pidemio/1984; 119: 71-80. levels of sex hormones, 30~' the association between 5 Krotkiewski M, Bjorntorp P, Sjostrom L, Smith U. Impact of obesity on metabolism in men and women. J Clin Invest 1983; 72: 1150-1162. and a decreased BMD, noted in the 6. Bjornlorp P. Obesity and the risk 01 cardiovascular disease. Ann Clin Res 1985; present study, may not be surprising. 17: 3-9. 7. Tonkelaar ID, Seidell JC, Van Noord PAH, Baanders-van Halewijn EA, Ouwehand Women with upper body obesity have increased serum IJ. Fat distribution in relation to age, degree of obesity, smoking habits. parity free and decreased sex hormone-binding and use: a cross-sectional study in 11 825 Dutch women participating in the DOM-project.ln! J Obes 1990; 14: 753-761. globulin levels.8-11.:l2-34 Conversely, the serum and tissue levels 8. BjOrntorp P. The association between obesity, adipose tissue distribution and of oestrogens and progesterone seem to be related to lower disease. Acta Med Scand 1988; 723: suppl. 121-134. 9. Aebuffe-Scrive M, Lonnroth P, Marin P, Wesslau C, Bjorntorp P, Smith U. Regional body fat accumulation with little influence on truncal­ adipose tissue metabolism in men and postmenopausal women.lnt J Obes 1987; abdominal fat. 55 Abdominal adiposity is also observed in 11:347-355. 10. Ley CJ, Lees B, Stevenson JC. Sex- and menopause-associated changes in hyperandrogenic conditions like the polycystic ovary body-fat distribution. Am J CUn Nurr 1992; 55: 950-954, 4 35 syndrome,30: idiopathic hirsutism ,8.34,36 and the menopause. n. Kirschner MA, Samojlik E, Oreijka M, Sxmal E, Schneider G, Enel N. Androgen­ estrogen metabolism in women with upper body versus lower body obesity. J In women with an android fat distribution there is evidence CUn Endocrinol Metab 1990; 70: 473-479. of decreased sex steroid secretion, which may result from 12. Campaigne BN. Body fat distribution in females: metabolic consequences and implications for weight loss. Med Sci Sports &erc 1990; 22: 291-297. 25 aberrations of gonadotrophin release. Moreover, 13. Leibel Rl, Edens NK, Fried SK. Physiologic basis for the control of body fat hypercortisolaemia is known to decrease circulating levels of distribution in humans. Annu Rev NUIr 1989; 9: 417-443. 14. Johnston CC, Melton U Ill, Undsay R, Eddy O. Clinical indications for bone 30 female sex hormones. In men, central obesity is associated mass measurement. J Bone Miner Res 1989: 4: suppl 2, 1-28. 31 15. Gibson AS. Principles of Nutritional Assessment. New York: Oxford University with ageing, low levels of testosterone ,3l1 and increased Press, 1990. l1 peripheral aromatisation of androgens to oestrogens. .35 In 16. Frisancho AA, Flegel PN. Elbow breadth as a measure of frame sixe for US males both sexes, upper body obesity therefore seems to be and females. Am J C/in Nurr 1983; 37: 311-314. 17. Aosner B. Fundamentals of BiostatIstics. 2nd ad. Boston: Duxbury Press, 1986 associated with relative hypercortisolism and decreased sex 18. Slemenda CW. Hui Sl, Williams CJ, Christian JC, Meaney FJ, Johnston CC jun. hormone levels. Oestrogen deficiency is a known risk factor Bone mass and anthropometric measurements in adult females. Bone Miner 1990; 11: 101-109. for the development of GP in women. The effect of 19. Dawson-Hughes B, Shipp C, Sadowski L, Dallal G. Bone density of the radius, oestrogen on bone was initially thought to be indirectly spine and hip in relation to percentage of ideal body weight in post-menopausal women. Calcif Tissue Int 1987; 40: 310-314. mediated via its activation of vitamin 0 metabolism, 20. Felsen OT, lhang Y, Hannan MT. Anderson JJ. Effects of weighl and body mass stimulation of intestinal calcium absorption, or increase in index on bone mineral density in men and women: The Framingham Study. J Bone Miner Res 1993: 8: 567-573.

SAMJ Volume- 86 No. 9 September 1996 .. 21. Myburgh KH, Noakes TO. Roodt M, Hough FS. Effect 01 ellercise on the development of osteoporosis in adutt rats. J ;,ppl PhysJoJ 1989; 66: 14-19. 22. Longcope C. Kato T, Horton R. COnversion of blood androgens to esuogen in Formulary and funding normal adult men and women_ J Clin Invest 1969; 48; 2191-2201 23. Myburgh KH. Hutchins J, Fataar AS. Hough F5, Noakes TO. Low bone C1enslty is an etiologic factor for suess. fractures i" athletes. Ann Imern Med 1990; 113, implications of the gap 7~-759. 24. A$hwell M, Cole TJ. o.)(on AK. Obesity: new ltlsight IntO the anthropometric classification of fat diStribution shown by computed tomography. BMJ 1985; 290: between the national 1692-1694. 25. BjOrntorp P. Meta/)olic implications of t:lody fat distribution. Diabetes Care 1991: 14: 1132-1 t43. Essential Drugs List and 26. BjOrntorp P, Onosson M, Rebuffe-Scrive M, Xu X. Regional obesity and steroid hormone interactions In human adipose tissue. UCLA Symp Cell BiOi 1990: 132: 147-158. current prescribing in a 27. Br6nnegard M. Arner P. HellstrOm L Akner G. Guslafsson JA. Glucocorticoid receptor messenger nbonucleic acid ,n different regIons of human adipose tJssue. Endocrinology 1990: 127; 1689-1696. large health maintenance 28. Dempster DW. Arlat MA, MelJnier PJ. Mean wa/llhickness and fo.matIO" periods of uabecular bone packets in corticosterOId-induced Osteoporosis. Calcif TIssue In! 1983; 35: 410-417. organisation 29. Luken BP, Rain LG. Glucocorticoi(l-Induced OSIeoporosis: pathogenes;s and managemem. Ann Imern Med 1990; 112: 352-364. 30. Crilly RG, Cawood M. Marshall OH. NOTdin 6EC. Hormonal status in normal. Alan D. Rothberg, Laubi Waiters osteoporotic and corticosteroid-treated postmenopausal women. J R Soc Med 1989: 71: 733-736. 31. Goulding A, Gold E. Effects of chronic prednisolone treatment on bone resorption and bone composition in intact and ovariectomized rats and in ovariectomized Background. The Department of Health has prepared an rats receiving IJ-estradiol. Endocrinology 1988: 122: 482·487. 32. Evans DJ, Hoffmatln AG, Kalkhoff AK, Kissebah AH. Relationship of androgenic Essential Drugs Ust (EDL) for public sector activity to body fat topography, fat cell morphology and metabolic aberrations in implementation in 1996 and future extension to the private premenopausal women. J CHn Endocnnol Melao 1983: 57: 304-310. 33. Schapira DV, Kumar NG, Lyman GH. Obesity, body fat distribution and sex sector. Stakeholders have been consulted to ensure that hormones in breast cancer patients. Cancer 1991: 67: 2215-2218. 34. Evans DJ, Barth JH. Surke CW. Body fat topography m women with androgen the EDL achieves its objectives of safety, efficacy and excess./nr J Obes 1988; 12; 157-162. 35. SouchaTd C. Despres J. Mauriege P. Genetic and non-genetic determi"ants of quality at the lowest possible cost, while providing regional fat distribution. Endocr Rev 1993: 14: 72-93. coverage for 90 - 95% of the common and important 36. Hauner H. Ditschuneit HH, Pal 56, Moncayo R, Pfeiffer EF. Fat distribution, endocrine and metabolic profile in obese women wi1h and without hirsuflsm. conditions in the country. Merabolism 1988: 37: 281-286. 37. Schneidl!f G, Kirschner MA, BerkowiU A, Erte1 NH. Increased estregen This study was undertaken to gain insight into the current production in obese men. J Clin Endocrinol Metab 1979; 48; 633-638. use of EDL products by 200 general practitioners (GPs) 38. Zumoff 8. Hormonal abnormalities i" obesity. Acta Med SClUld 1988: 723: suppl, 153,160. servicing a large health maintenance organisation (HMO). 39. Erikseo EF. ,""osekllde L and bone. In: Hursche JNM, Kanis JA, eels. Bone and Mineral ReseMch- Vot 7. Amsterdam: Elsevlef Science Pubhshers. Methods. Approximately 120 000 prescriptions were 1990: 273-312. 40. Gteenspan SL. Oppenheim OS, KJibanski A. Importance 01 gOl'ladal steroids to reviewed and the use of specified EDL , other bone mass in men with hyperprolactinemic hypogonadism. Ann Intem Med 1989; forms of EDL medicines and non-EDL medicines was 110: 526-531. 41. Hasstedt SJ. Ramlrez ME, Kuida H. Williams RA. Recessive inheritance of a analysed for several pharmacological groups. These relative fat panern. Am J Hum Gener 1989; 45: 917-925. included antibiotics and medicines for the cardiovascular, Accepted 8 June 1995. musculoskeletal, central nervOUS r respiratory and gastro­ intestinal systems. To gauge potential savings to the private sector through the purchase of EDL products at state tender prices, current prices of a random sample of EDL products were compared. Results. In the areas reviewed, only 22.4% of current GP prescriptions included EDL items; a further 19.6% included 'other forms of EDL' items. Simply obtaining those EDl products that are currently prescribed at state tender prices would recluce costs by almost 20%, while extending the use of EDl products might save in excess of 70% on private sector GP prescriptions. Conclusions. Assuming that all prescriptions were clinically indicated, the 'gap' between the EDL and medicines prescribed indicates that debate will be

Department of Paediatrics, University of the Witwatersrand, Johannesburg

Alan O. Rothberg. M.a. a.CH.. F.C.P. (SA). PH.O

Pharmaceutical Benefit Management (Pty) Ltd, Cape Town Laubi Wafters. M.8 0'-6_. MPHAAM MED.

Volume 86 No.9 Sepumbtr 1996 SAMJ