Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health, vol. 16, no. 3, 353e359, 2013� Copyright 2013 by The International Society for Clinical Densitometry1094-6950/16:353e359/$36.00

http://dx.doi.org/10.1016/j.jocd.2012.08.074

Original Article

Relationship of Body Fat and Its Distribution With Bone MineralDensity in Indian Population

Raman Kumar Marwaha,*,1 Mahendra K. Garg,2 Nikhil Tandon,3 Neena Mehan,4

Aparna Sastry,1 and Kuntal Bhadra1

1Department of Endocrinology and Thyroid Research Centre, Institute of Nuclear Medicine & Allied Sciences, Timarpur,New Delhi 110054, India; 2Department of Endocrinology and Metabolism, Army Hospital (Research & Referral), DelhiCantonment, New Delhi, India; 3Department of Endocrinology and Metabolism, All India Institute of Medical Sciences,

New Delhi, India; and 4Department of Medicine, B. R. Sur Institute of Homeopathy, New Delhi, India

Abstract

ReRK*A

Departute of11005

Obesity has been associated with increased bone mineral density (BMD). There is evidence of differential effectof regional fat on BMD. Hence, we undertook this study to evaluate the correlation between total body fat and itsdistribution with BMD in nonobese (mean body mass index: 25.0� 4.7 kg/m2) Indian adult volunteers. A total of2347 participants (men: 39.4% and women: 60.6%) included in this cross-sectional study were divided according tosex and age. Fasting blood samples were drawn for biochemical parameters. Percent total body, truncal, and leg fatand BMD at lumbar spine, femur, and forearm were measured by dual-energy X-ray absorptiometry. The BMD at allsites (radius, femur, and spine) increased from lowest to highest quartiles of percent body fat. Percent truncal fat waspositively correlated with BMD at all sites in both sexes, except for femoral neck in men, where it had negativecorrelation. Percent leg fat was positively related with BMD at all sites in premenopausal women, and spine andradius BMD in postmenopausal women. However, in men, it had negative correlation with femoral neck BMD.On multiple regression analysis, regional fat had positive association with BMD at all sites after adjusting forage, sex, lean mass index, 25-hydroxyvitamin D, and intact parathyroid hormone levels. Leg-to-total body fat ratiowas negatively associated with BMD at all sites in men and pre- and postmenopausal women. Percent total body andregional fat have positive association with BMD at all sites in men and women.

Key Words: Bone mineral density; DXA; leg fat; total body fat; truncal fat.

Introduction

Obesity, as assessed by body mass index (BMI), has beenreported to be protective for osteoporotic fractures and asso-ciated with increased bone mineral density (BMD) (1e4).Body mass consists of bone, as well as lean and fat mass.Fat mass may affect BMD by mechanical loading, and vari-ous adipokines and cytokines secreted by adipocytes may

ceived 06/20/12; Revised 07/30/12; Accepted 08/02/12.M and MKG are joint first authors.ddress correspondence to: Raman Kumar Marwaha, MD, DM,tment of Endocrinology and Thyroid Research Centre, Insti-Nuclear Medicine and Allied Sciences, Timarpur, New Delhi4, India. E-mail: marwaha_ramank@hotmail.com

353

also interact with bone cells (3,4). Many studies have beenpublished to dissect differential effect of fat mass on BMD(5e26). Furthermore, there is evidence of differential effectof regional fat on BMD, that is, subcutaneous and visceralfat have positive and negative effects on BMD, respectively(21e24). Most of the studies have been performed inpostmenopausal women with or without osteoporosis (7,9e15,18,26) and few in premenopausal women (13,15,19,20)and men (5,6,12). Because fat mass and body weight are col-linearly related, it becomes relevant to evaluate the indepen-dent effect of fat mass on BMD. However, most publishedstudies have been unable to optimally explore the indepen-dent effects of fat mass on bone mass, as a consequence oftheir small sample size. In addition, although most studieshave used dual-energy X-ray absorptiometry (DXA) for

354 Marwaha et al.

measurement of body fat and its distribution (5e9,11,14e16,18e20,25,26), others have used quantitative com-puted tomography (QCT) (5,12), magnetic resonance imaging(24), electrical bioimpedance (9,13), or calculated fat basedon anthropometry (17).

There are ethnic differences in fat distribution, which hasbeen recognized by International Guidelines (27). BecauseIndians have higher body fat (28) and lower BMD (29) com-pared with Caucasians, we designed this cross-sectional pop-ulation-based study to evaluate the relationship between fatmass and its regional distribution with BMD.

Materials and Methods

This study was carried out as part of voluntary generalhealth checkup of all members of the Resident Welfare As-sociations of 4 residential colonies, 1 each from North,South, East, and West Delhi in the year 2009e2011. Thestudy included all participants aged older than 20 yr (men:39.4% and women: 60.6%) excluding those with infectious,hepatic, renal, neoplastic, gastrointestinal, dermatological,and endocrine disorders; steroid intake; or alcoholism. De-mographic, anthropometric, and clinical data were ascer-tained and a detailed physical examination conducted. Allparticipants were divided into 2 groups: group 1 (�50 yr)and group 2 (O50 yr) so that all premenopausal womenfall in group 1 and postmenopausal in group 2. The BMIwas calculated by weight in kilogram divided by square ofheight in meters. The BMI has element of fat and bone in-corporated; hence, we calculated ‘‘fat-free mass index’’(FFMI) by dividing fat-free weight (weight� total bodyfat) by square of height in meters, where total body fatwas calculated as percent total fat�weight divided by100; and ‘‘lean BMI’’ (LMI) by deducting fat mass andbone mass (total bone mineral content) from weight. Thiswas done to remove duplication of fat and bone data in mul-tiple regression analysis.

Fasting blood samples were drawn for the estimation of se-rum 25-hydroxyvitamin D [25(OH)D]; intact parathyroid hor-mone (iPTH); and total and ionized calcium, inorganicphosphorus, and alkaline phosphatase (ALP). The study wasapproved by the ethics committee of the Institute of NuclearMedicine and Allied Sciences and all participants gave writ-ten informed consent.

The normal range for different biochemical parameters areas follows: serum total calcium (2.2e2.55 mmol/L), ionizedcalcium (1.12e1.32 mmol/L), phosphate (0.9e1.5 mmol/L),and ALP (women: !240 U/L and men: !270 U/L). Theserum concentrations of 25(OH)D (reference range:22.5e94 nmol/L) and iPTH (reference range: 10e65 ng/L)were measured by radioimmunoassay (Diasorin, Stillwater,MN) and electrochemiluminescence assay (Roche Diagnos-tics GmbH, Manheim, Germany), respectively.

The BMD at anteroposterior lumbar spine (L1eL4), femur(total hip and femoral neck), forearm (33% radius), and totalbody was measured using the Prodigy Oracle (GE Lunar,Corp., Madison, WI) according to standard protocol. Quality

Journal of Clinical Densitometry: Assessment & Management of Muscu

control procedures were carried out in accordance with themanufacturer’s recommendations. Instrument variation wasdetermined regularly using a phantom supplied by the manu-facturer and mean coefficient of variation was !0.5%. Forin vivo measurements, mean coefficients of variation for allsites were !1%.

Body fat mass and regional distribution was measured us-ing the same DXA machine. Instrument variation was deter-mined by measuring total body fat mass and regional fatmass in 20 healthy adults twice and mean coefficient of var-iation was !0.5%. Percent fat were measured for total body,trunk, arms, and legs. All participants were divided in quar-tiles of percent total and regional fat to assess impact onBMD at total body and individual sites. Percent leg fat andleg fat-to-total fat ratio (LTR) were considered as indicativeof subcutaneous fat; and percent trunk fat and trunk fat-to-total fat ratio (TTR) indicative of visceral fat.

Statistical analysis was carried out using EPI INFO 3.5.3(CDC, Atlanta, GA). Data were presented as mean� standarddeviation or number (%) unless specified. All parametric datawere analyzed by Student’s t-test. If Barlett’s Chi-square testfor equality of population variances was !0.05, thenKruskal-Wallis test was applied. All nonparametric datawere analyzed by Chi-square test. Multiple regression analy-sis was done to ascertain association between total fat and itsdistribution with BMD at various sites after adjustment withvariables such as age, BMI (FFMI or LMI), serum ionizedcalcium, phosphate, ALP, 25(OH)D, and iPTH levels. Pear-son’s correlation coefficient was calculated to assess thestrength of relationship between total fat and its distributionand BMD at various sites. A p value lower than 0.05 was con-sidered statistically significant.

Results

This study included 2347 participants aged older than20 yr (men: 39.4% and women: 60.6%). Mean age andBMI were 49.1� 18.2 yr (range: 21e90 yr) and 25.0�4.7 kg/m2 (range: 13.0e49.8 kg/m2), respectively. Men wereolder than women (54.0� 16.7 vs 45.9� 18.5; p!0.00001). Total population was divided and grouped for anal-ysis into men, and women aged younger than 50 yr (premen-opausal) and older than 50 yr (postmenopausal). Basiccharacteristics of the population are given in Table 1.

Men

The BMD at all sites increased from lowest to highestquartiles of percent total fat (Table 2). On adjusting forBMI, the relationship between percent body fat and BMDbecame negative. However, if BMI was replaced with eitherFFMI or LMI, a positive relationship reemerged betweenpercent body fat and BMD. Both markers of visceral fat, per-cent trunk fat and TTR, were negatively correlated with BMDat femoral neck and positively with spine and radius BMD.Although LTR was negatively correlated with BMD at allsites, the other surrogate for subcutaneous fat, namely percent

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Table 1Basic Characteristics of the Population

Characteristics

Men Women

!50 yr O50 yr p Value !50 yr O50 yr p Value

Number (%) 559 (60.5) 365 (39.5) 788 (55.4) 635 (44.6)Age (yr) 36.1� 9.1 65.8� 7.5 31.0� 8.6 64.5� 7.4Height (cm) 171.9� 7.1 165.8� 6.1 !0.0001 159� 5.9 153� 6.0 !0.0001Weight (kg) 71.2� 13.0 70.1� 12.3 0.20 57.6� 10.2 65.9� 12.1 !0.0001BMI (kg/m2) 24.1� 4.0 25.5� 4.0 !0.0001 22.8� 4.1 28.0� 4.9 !0.0001Lean weight (kg) 44.3� 7.5 43.6� 5.6 0.01 33.6� 4.4 33.0� 4.8 0.001Lean BMI (kg/m2) 15.0� 2.5 15.8� 1.6 !0.0001 13.3� 1.6 14.0� 1.8 !0.0001Serum calcium 9.7� 0.5 9.7� 0.4 0.11 9.7� 0.5 9.7� 0.4 0.20Ionized calcium 1.14� 0.07 1.15� 0.05 0.0009 1.14� 0.03 1.15� 0.05 0.0002Serum phosphate 3.5� 0.05 3.5� 0.05 0.84 3.8� 0.05 3.8� 0.05 0.12ALPa 189� 51 (182) 222� 88 (205) !0.0001 220� 80 (206) 244� 88 (228) !0.0001Serum 25(OH)Da 9.8� 6.5 (8.7) 8.9� 6.5 (7.2) 0.041 7.0� 4.2 (6.2) 9.1� 7.1 (7.0) 0.0001PTHa 41.1� 29.8 (33.4) 60.4� 32.6 (55.4) !0.0001 49.1� 26.5 (44.8) 59.7� 35.2 (54.7) !0.0001

Abbr: 25(OH)D, 25-hydroxyvitamin D; ALP, alkaline phosphatase; BMI, body mass index; PTH, parathyroid hormone; SD, standard de-viation.

aValues are expressed as mean� SD (median).

Fat and BMD 355

fat at legs, was negatively correlated only with femoral neckBMD (Table 3).

In multiple regression analysis, after adjusting for age,BMI, serum ionized calcium, phosphate, ALP, 25(OH)D,and iPTH levels, visceral fat was negatively associated onlywith femoral neck BMD, whereas subcutaneous fat had neg-ative association at all sites (Table 4). However, when BMIwas substituted with either FFMI or LMI, visceral fat waspositively associated with BMD at all sites (Table 5 andTable 6). Although percent leg fat was positively associated

TableBMD (g/cm2) in Participants With

Parameters First quartile Second

Femoral neck BMDa

Men 0.945� 0.163 0.949Women (!50 yr) 0.958� 0.118 0.972Women (O50 yr) 0.802� 0.159 0.808

Spine (L1eL4) BMDb

Men 1.067� 0.156 1.110Women (!50 yr) 1.080� 0.128 1.103Women (O50 yr) 0.925� 0.203 0.955

Radius 33% BMDc

Men 0.709� 0.090 0.724Women (!50 yr) 0.648� 0.088 0.655Women (O50 yr) 0.566� 0.101 0.579

Abbr: BMD, bone mineral density.aStatistically significant difference ( p! 0.05) between first and thirdbStatistically significant difference ( p! 0.05) between all quartiles ecStatistically significant difference ( p! 0.05) between all quartiles i

Journal of Clinical Densitometry: Assessment & Management of Muscu

with radius BMD, the negative association of LTR withBMD at all sites persisted.

Premenopausal Women (!50 yr)

The BMD at all sites increased from lowest to third quar-tiles, but this relationship did not persist in the highest quar-tile (Table 2). The relationship between percent total body fatand BMD became negative on adjusting for BMI, but a posi-tive relationship reemerged if BMI was replaced with eitherFFMI or LMI. The percent trunk fat and percent leg fat had

2Quartiles of Percent Total Fat

quartile Third quartile Fourth quartile

� 0.154 0.962� 0.138 0.991� 0.161� 0.122 1.005� 0.116 0.995� 0.141� 0.125 0.834� 0.141 0.860� 0.150

� 0.172 1.144� 0.176 1.145� 0.163� 0.126 1.136� 0.114 1.136� 0.141� 0.158 0.993� 0.141 1.019� 0.147

� 0.067 0.728� 0.065 0.745� 0.093� 0.060 0.664� 0.059 0.669� 0.086� 0.095 0.594� 0.082 0.621� 0.113

/fourth quartiles.xcept third and fourth quartiles.n men; and between first and third/fourth quartiles in women.

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Table 3Correlation of Fat Distribution With BMD

ParametersPercent fat trunk,r value ( p value)

Trunk-to-total ratio,r value ( p value)

Percent fat legs, r value( p value)

Legs-to-total ratio,r value ( p value)

MenFemoral neck �0.162 (!0.0001) �0.157 (!0.0001) �0.170 (!0.0001) �0.155 (!0.0001)Spine L1eL4 0.134 (!0.0001) 0.085 (0.009) 0.044 (0.17) �0.091 (0.005)Radius 33% 0.160 (!0.0001) 0.072 (0.026) 0.063 (0.068) �0.087 (0.007)

Women (!50 yr)Femoral neck 0.243 (!0.0001) 0.028 (0.47) 0.180 (!0.0001) �0.028 (0.47)Spine L1eL4 0.280 (!0.0001) 0.145 (0.0002) 0.155 (!0.0001) �0.138 (0.0004)Radius 33% 0.243 (!0.0001) 0.076 (0.05) 0.289 (!0.0001) �0.103 (0.009)

Women (O50 yr)Femoral neck 0.138 (0.0001) 0.145 (!0.0001) 0.056 (0.11) �0.123 (0.0005)Spine L1eL4 0.207 (!0.0001) 0.118 (0.0009) 0.124 (0.0004) �0.098 (0.005)Radius 33% 0.107 (0.002) 0.069 (0.051) 0.083 (0.01) �0.078 (0.026)

Abbr: BMD, bone mineral density.

356 Marwaha et al.

positive correlation with BMD at all sites. However, TTR waspositively correlated and LTR negatively correlated withBMD at spine and radius (Table 3).

In multiple regression analysis, after adjusting for age,BMI, serum ionized calcium, phosphate, ALP, 25(OH)D,and iPTH levels, percent trunk fat was positively associatedwith spine BMD, whereas TTR had a weak positive associa-tion with femoral neck BMD. Percent leg fat was negativelyassociated with BMD at femoral neck and radius. However,LTR was not correlated with BMD at any site (Table 4). Sim-ilar to men, when BMI was substituted with either FFMIor LMI, visceral fat and percent leg fat was positively

TableMultiple Regression Analysis of Percent Fat Distribution (Subcu

BMI, Ionized Calcium, Phosphate, ALP

Parameters

Percent fat trunk Trunk-to-total f

Coefficient ( p value) Coefficient ( p

MenFemoral neck �0.001 (0.07) �0.009 (0.8Spine L1eL4 0.00 (0.82) 0.087 (0.1Radius 33% 0.00 (0.22) 0.055 (0.0

Women (!50 yr)Femoral neck �0.001 (0.52) 0.208 (0.0Spine L1eL4 0.002 (0.008) 0.142 (0.2Radius 33% 0.00 (0.48) 0.008 (0.9

Women (O50 yr)Femoral neck 0.003 (0.001) 0.004 (0.9Spine L1eL4 0.006 (!0.0001) 0.393 (0.0Radius 33% 0.001 (0.36) 0.078 (0.2

Abbr: 25(OH)D, 25-hydroxyvitamin D; ALP, alkaline phosphatase; Bhormone.

Journal of Clinical Densitometry: Assessment & Management of Muscu

associated, and LTR remained negatively associated withBMD at all sites (Tables 5 and 6).

Postmenopausal Women (O50 yr)

The BMD at all sites increased from lowest to highestquartiles of percent total fat (Table 2). A similar trend wasobserved in relationship between percent total body fat andBMD as seen in women aged younger than 50 yr. Visceralfat and percent leg fat had positive correlation, whereasLTR was negatively correlated with BMD at all sites(Table 3).

4taneous and Visceral) and BMD (After Adjustment for Age,, PTH, and Serum 25(OH)D Levels)

at ratio Percent leg fat Leg-to-total fat ratio

value) Coefficient ( p value) Coefficient ( p value)

6) �0.003 (0.005) 0.01 (0.81)8) �0.003 (0.0009) �0.128 (0.10)6) �0.001 (0.0006) �0.012 (0.009)

5) �0.002 (0.004) �0.168 (0.12)8) 0.00 (0.85) �0.106 (0.34)0) �0.001 (0.04) �0.047 (0.48)

6) 0.00 (0.80) �0.04 (0.70)09) �0.001 (0.50) �0.424 (0.007)6) �0.002 (0.01) �0.151 (0.03)

MD, bone mineral density; BMI, body mass index; PTH, parathyroid

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Table 5Multiple Regression Analysis of Percent Fat Distribution (Subcutaneous and Visceral) and BMD (After Adjustment for Age,

FFMI, Ionized Calcium, Phosphate, ALP, PTH, and Serum 25(OH)D Levels)

Parameters

Percent fat trunk Trunk-to-total fat ratio Percent leg fat Leg-to-total fat ratio

Coefficient ( p value) Coefficient ( p value) Coefficient ( p value) Coefficient ( p value)

MenFemoral neck 0.001 (0.004) 0.027 (0.61) 0.001 (0.21) �0.015 (0.81)Spine L1eL4 0.003 (!0.0001) 0.026 (0.06) 0.001 (0.18) �0.163 (0.05)Radius 33% 0.002 (!0.0001) 0.064 (0.04) 0.006 (0.004) �0.093 (0.01)

Women (!50 yr)Femoral neck 0.003 (!0.0001) 0.380 (0.0002) 0.002 (0.003) �0.304 (0.004)Spine L1eL4 0.004 (!0.0001) 0.335 (0.001) 0.003 (!0.0001) �0.205 (0.01)Radius 33% 0.001 (0.015) 0.07 (0.24) 0.001 (0.11) �0.094 (0.15)

Women (O50 yr)Femoral neck 0.003 (!0.0001) 0.022 (0.82) 0.002 (0.02) �0.046 (0.66)Spine L1eL4 0.007 (!0.0001) 0.426 (0.0004) 0.003 (0.001) �0.435 (0.0007)Radius 33% 0.002 (!0.0001) 0.084 (0.23) 0.001 (0.051) �0.138 (0.062)

Abbr: 25(OH)D, 25-hydroxyvitamin D; ALP, alkaline phosphatase; BMD, bone mineral density; FFMI, fat-free mass index; PTH, para-thyroid hormone.

Fat and BMD 357

In multiple regression analysis, after adjusting for age,BMI, serum ionized calcium, phosphate, ALP, 25(OH)D,and iPTH levels, visceral fat was positively associated withfemoral neck and spinal BMD. Both markers for subcutane-ous fat were negatively associated with BMD at radius(Table 4). When BMI is substituted with either FFMI orLMI, there was similar association of visceral fat and percentleg fat with BMD as in women aged younger than 50 yr(Tables 5 and 6). The LTR remained negatively associatedwith BMD at all sites.

TableMultiple Regression Analysis of Percent Fat Distribution (Subcu

LMI, Ionized Calcium, Phosphate, ALP

Parameters

Percent fat trunk Trunk-to-total f

Coefficient ( p value) Coefficient ( p

MenFemoral neck 0.002 (0.001) 0.042 (0.43)Spine L1eL4 0.003 (!0.0001) 0.152 (0.026Radius 33% 0.002 (!0.0001) 0.072 (0.027

Women (!50 yr)Femoral neck 0.003 (!0.0001) 0.405 (!0.0Spine L1eL4 0.004 (!0.0001) 0.362 (0.000Radius 33% 0.001 (0.006) 0.084 (0.18)

Women (O50 yr)Femoral neck 0.004 (!0.0001) 0.035 (0.72)Spine L1eL4 0.007 (!0.0001) 0.444 (0.000Radius 33% 0.003 (!0.0001) 0.093 (0.19)

Abbr:; 25(OH)D, 25-hydroxyvitamin D; ALP, alkaline phosphatase; Bhormone.

Journal of Clinical Densitometry: Assessment & Management of Muscu

Discussion

Although it is well known that BMI is positively associatedwith BMD across all ages (1e4), the effect of fat mass and itsregional distribution on BMD remains controversial (5e26).In the present large population-based cross-sectional study,we found that BMD at spine, femoral neck, and radius in-creased from lowest to highest quartiles of total percentbody fat. Similar to our results, a Dutch study also reporteda positive correlation of fat distribution and BMD, which

6taneous and Visceral) and BMD (After Adjustment for Age,, PTH, and Serum 25(OH)D Levels)

at ratio Percent leg fat Leg-to-total fat ratio

value) Coefficient ( p value) Coefficient ( p value)

0.001 (0.17) �0.034 (0.03)) 0.001 (0.12) �0.195 (0.01)) 0.001 (0.002) �0.101 (0.008)

001) 0.002 (0.002) �0.331 (0.002)8) 0.003 (!0.0001) �0.294 (0.004)

0.001 (0.09) �0.104 (0.01)

0.002 (0.02) �0.065 (0.05)2) 0.003 (0.001) �0.461 (0.0003)

0.001 (0.04) �0.150 (0.044)

MD, bone mineral density; LMI, lean mass index; PTH, parathyroid

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358 Marwaha et al.

became negative after adjustment for BMI in both sexes (7).A similar observation was made by a Korean study amongperimenopausal women after adjustment for age and weight(15). However, in contrast, a study from United States re-ported an inverse association between total fat mass withwhole body bone mineral contents (10).

The relationship between fat and BMD after adjustmentfor weight and BMI has been criticized (30), as both theseparameters have total fat mass already incorporated inthem. Hence, these studies (7,14,15) report deleterious effectof fat mass on BMD. We also showed that relationshipbetween fat mass and BMD becomes negative when adjustedfor BMI in multiple regression analysis (Table 4). Previ-ously, other authors have also evaluated the relationship be-tween BMD and fat-free mass, lean mass, and FFMI (5e7,19,25,26). The regression analysis between fat-free massand BMD is confounded by the fact that fat-free mass in-cludes bone weight, which is related to BMD. To circumventthis, we have substituted BMI with both FFMI and LMI,while evaluating the association between fat and BMD,and found that this relationship became positive on usingFFMI (Table 5) and further strengthened when LMI wasused (Table 6).

Another finding that surprised us was the constant negativeassociation of LTR with BMD at all sites in all groups. A sim-ilar observation has been made in young women (31). Wespeculate that LTR is an indicator of physical activity. Phys-ical inactivity leads to accumulation of fat in legs, which hasbeen clearly documented in participants with stroke, wherethe paralytic leg has significantly more fat mass comparedwith the nonparalytic leg (32). Participants undergoing resis-tance training have more fat-free mass and lesser fat in legs(33). Lower extremity muscle mass predicts the functionalperformance in elderly participants (34). Hence, lower LTRwill be related to higher amounts of physical activity, whichis known to increase bone mass (35). Hence, this will explaininverse relation between LTR and BMD. Although we havenot collected data on physical activity in this study, if thisrelation is confirmed in future studies, the LTR can be consid-ered an objective parameter of physical activity in a nonobeseIndian population.

Because many studies have highlighted a differential rela-tionship between body fat and BMD based on sex and meno-pausal status, we performed additional analysis to address thisissue.

Men

In the present study, BMD at all sites increased with in-creasing quartiles of percent body fat. Visceral (trunk fat)and subcutaneous (leg) fat were negatively correlated withBMD at femoral neck and positively with BMD at spineand radius. However, after adjustment with age; serum ion-ized calcium, phosphate, ALP, 25(OH)D, and iPTH levels;and LMI, truncal fat was positively associated with BMDat all sites. It has been reported that visceral fat is inverselyassociated with BMD at femoral neck in older adult males(8). In the Tobago bone health study among middle-aged

Journal of Clinical Densitometry: Assessment & Management of Muscu

and elderly Afro-Caribbean men from United States, leglean mass fraction and total body fat mass fraction had sig-nificant and opposing effects at the femur BMD (36). Con-trary to this, an observational cohort study from Koreareported no significant correlation between fat and boneparameters in men (14). In a population-based study amongolder men (O40 yr), higher total adipose area measured byQCT was associated with lower cortical BMD and higherpercent subcutaneous adipose tissue with greater corticalBMD (37).

Premenopausal Women (!50 yr)

In the present study, BMD at all sites increased from low-est to third quartiles, but this relationship did not persist in thehighest quartile. Truncal and leg fat had positive correlationwith BMD at all sites, which persisted after adjustment forthe above-mentioned parameters. Earlier studies have shownthat BMD is positively related with total fat mass (17), fatmass index (21), and visceral fat (22). In contrast, although2 other studies report an absence of relationship between fatmass and BMD in young healthy nonobese (20) and premen-opausal women (14), other investigators have also reported aninverse relationship between visceral fat and BMD in adoles-cent girls and premenopausal women (5,15,25). However,these studies have been criticized for using BMI and weightfor adjustment in regression analysis (30).

Postmenopausal Women (O50 yr)

Percent total fat, truncal fat, and leg fat was positively cor-related with BMD at all sites, which persisted even after ad-justment for age; serum ionized calcium, phosphate, ALP,25(OH)D, and iPTH levels; and LMI. Most investigatorshave also reported that fat mass is an independent predictorof BMD at individual or multiple sites (9,11,12,17,26). Stud-ies have also demonstrated a positive relationship betweenBMD at various sites and truncal (13,18) as well as leg fat(13). In contrast, other studies found no significant correla-tion between fat and bone parameters in postmenopausalwomen (14,16,20,38). However, a population-based studyobserved that fat mass and waist hip ratio had negative cor-relation with lumbar spine BMD after adjustment with ageand weight (15).

The main limitation of the study was absence of longitudi-nal data, which would have allowed assessment of the changein body fat and its effect on BMD. Another limitation was ab-sence of measurement of adipokines, which could have high-lighted the mechanism of association between body fat andBMD. However, the strength of the study was its large samplesize from a healthy Indian population.

In conclusion, percent total body and truncal fat have pos-itive association with BMD at all sites in men and pre- andpostmenopausal women in nonobese healthy Indians. TheLTR is negatively correlated with BMD at all sites. This ob-servation merits future studies involving concurrent evalua-tion of physical activity scores to help establish LTR asa marker of physical inactivity.

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Fat and BMD 359

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loskeletal Health Volume 16, 2013