Does Bone Loss Begin After Weight Loss Ends?

Results 2 Years After Weight Loss or Regain in Postmenopausal Women

Nancy L. Von Thun, MS; Deeptha Sukumar, PhD; Steven B. Heymsfield, MD; Sue A. Shapses, PhD

Menopause. 2014;21(5):501-508. 

Abstract and Introduction

Abstract

Objective. Short-term weight loss is accompanied by bone loss in postmenopausal women. The longer-term impact of weight loss on bone in reduced overweight/obese women compared with women who regained their weight was examined in this study using a case-control design.

Methods. Postmenopausal women (N = 42; mean [SD] body mass index, 28.3 [2.8] kg/m2; mean [SD] age, 60.7 [5.5] y) were recruited 2 years after the start of a 6-month weight loss trial; those who maintained their weight (weight loss maintainer [WL-M] group) were matched to a cohort of women who regained their weight (weight loss regainer [WL-R] group). Serum hormones and bone markers were measured in a subset. Bone mineral density (BMD) at the femoral neck, trochanter, spine, radius, and total body, and soft-tissue composition were taken at baseline, 0.5 years, and 2 years.

Results. During weight loss, both groups lost 9.3% (3.4%) of body weight, with no significant difference between the groups. After weight loss, weight change was −0.1% (2.7%) and 6.0% (3.3%) in the WL-M (n = 22) and WL-R (n = 20) groups, respectively. After 2 years, both groups lost BMD at the femoral neck and trochanter (P ≤ 0.01), whereas only the WL-M group reduced BMD at the 1/3 radius (P < 0.001). There was greater BMD loss at the trochanter (−6.8% [5.7%]) and 1/3 radius (−4.5% [3.3%]) in the WL-M group compared with the WL-R group after 2 years. Multiple linear regression showed that change in leg fat mass (but not trunk fat) contributed to trochanter BMD loss (P < 0.05).

Conclusions. After 2 years, there is no BMD recovery of weight reduction-induced bone loss, irrespective of weight regain. These data suggest that the period after weight loss may be an important point in time to prevent bone loss for those who maintain weight and those who regain weight.

Introduction

Obese and overweight people are strongly encouraged to lose 5% to 15% of their weight to reduce the risk of comorbid conditions. During the menopausal transition, women tend to gain weight and visceral adiposity; therefore, many of these women who were never overweight previously are now encouraged to reduce weight to improve health. However, studies show that weight loss in even obese and overweight women results in bone mineral density (BMD) loss of approximately 1% to 2% with 10% weight reduction and can partially be attenuated with certain interventions.[1-4] Loss of bone due to weight reduction is more consistently shown in older individuals compared with younger individuals.[4-7] In large retrospective studies, weight reduction whether weight loss was voluntary or involuntary—has been associated with higher hip bone loss and fracture.[8-10]

Overweight and obese individuals who lose weight either maintain a reduced-obese state or regain lost weight primarily as fat mass.[11] Women who are restrained eaters, who go on long-term diet, or who "weight cycle" (weight loss followed by regain) may be at greater risk for low bone mass or osteoporosis.[10,12,13] A limited number of previous trials have examined response to weight regain after weight reduction in a single group of women to show that it leads to partial recovery of bone at some anatomical sites.[14-17] In this trial, we use a case-control design to examine whether the rate of bone loss differs in reduced-obese postmenopausal women who maintain their lost weight for 2 years compared with those who regain their lost weight.

Methods

Participants

Postmenopausal women who successfully completed a 6-month weight loss protocol in our laboratories were eligible for recruitment in this study. Participants were contacted approximately 2 years after their initial inclusion in a 6-month weight reduction program reported previously[1,2,18] or that was part of small unpublished pilot studies from 2002 to 2008. To be eligible, postmenopausal women had to be healthy—without evidence of osteoporosis, metabolic bone disease, thyroid disorders, immune disease, myocardial infarction, or stroke in the past 6 months, or without kidney stones, diabetes, active cancers, or cancer therapy within the past 12 months. Participants were excluded if they changed their usual daily intake of supplemental calcium or multivitamin/mineral, started a new exercise program, or were taking medications known to influence bone metabolism, including hormone therapy. These studies were approved by the Rutgers University Institutional Review Board. All participants signed an informed consent form.

Protocol

Participants were measured at three time points: baseline (time 0), 6 months of weight reduction (0.5 y), and final (2 y). During the weight loss period (0-0.5 y), participants underwent 6 months of weight loss interventions in our laboratories. In this protocol, participants were counseled—once weekly for the first 2 months and then twice monthly thereafter—by a registered dietitian to reduce their usual intake by 500 to 600 kcal/day while maintaining usual physical activity levels, as described previously.[1,2,18] During the 6-month intervention, volunteers were given a multivitamin containing 400 IU of vitamin D3, and total calcium intake was at least 1,000 mg/day in all women. Upon completion of the intervention, all participants were counseled to consume approximately 1.2 g of Ca and 400 IU of vitamin D daily through diet and supplementation. After weight loss, there was a nointervention period (0.5-2.0 y), and participants were categorized according to weight change for this final measurement. Women who maintained their weight were recruited and agematched to a cohort of women who did not meet these criteria and regained their body weight (weight loss regainer [WL-R]) in a case-control design. For eligibility in the weight loss maintainer (WL-M) group, weight regain needed to be less than 25%. The WL-R group was composed of those who regained more than this amount.

Bone and Body Composition Measurements and Serum Markers

Weight and height were measured to the nearest 0.25 kg and 0.25 cm, respectively, at baseline, after weight loss (0.5 y), and at the 2-year final measurement with a balance beam scale and a stadiometer, respectively (Detecto, Webb City, MO). BMD was measured at the femoral neck, trochanter, spine, total body, 1/3 radius, and ultradistal (UD) radius by dual-energy x-ray absorptiometry (DXA; GE Lunar, Madison, WI; coefficient of variation <1% for all sites). Scans were performed by using enCORE 2004 software (version 8.10.027; GE Lunar). Bone mineral content at each site was also measured. Fat-free soft tissue (FFST), total fat mass, trunk fat, and leg fat were measured by DXA using total body scans and the manufacturer’s standard cut lines for leg and trunk regions. Calcium intake was estimated using 3-day food records and analyzed using the US Department of Agriculture database (Food Works Software 10.1; Food Works, Long Valley, NJ).

Fasting morning blood samples were collected from the entire population at baseline and from a subset (n = 22) after 2 years. The bone formation marker osteocalcin (BTI, Stoughton, MA; coefficient of variation <9%) was measured by radioimmunoassay (RIA). Serum N-telopeptide of type I collagen was measured by enzyme-linked immunosorbent assay (Osteomark, Princeton, NJ; coefficient of variation <4.6%). Intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), and estradiol were analyzed by RIA. The coefficient of variation was less than 6.8% for PTH (DSL, Webster, TX; Scantibodies, Santee, CA), less than 12.5% for 25(OH)D (DiaSorin, Stillwater, MN), and less than 12.2% for estradiol (DSL, Webster, TX). Our laboratory participates in a vitamin D external quality assessment scheme (DEQAS) to monitor the performance of the RIA used for 25(OH)D assessment.

Statistical Analysis

Changes in body composition, hormones, and bone markers at the three time points (baseline, 0.5 y, and 2 y) between the groups (WL-R and WL-M) were analyzed by a two-factor repeated-measures analysis of variance (ANOVA). If the F test was significant, post hoc analysis was performed using Tukey’s pairwise multiple comparison. Changes in bone markers between the groups from baseline to final measurement were analyzed using one-way ANOVA. Annual BMD loss was determined at each site by dividing the percent change in BMD by the number of months during the entire study period for each individual. Multiple regression analysis was used to assess how the change in independent variables (age, leg fat, trunk fat, and FFST) across time influenced the change in BMD at each site. To determine whether weight loss and weight regain will have a similar effect on BMD, we performed a power analysis with α set to 0.05 and with β set to 0.90 using trochanter BMD change during weight loss or maintenance.[5] This analysis indicated that 15 participants per group would be necessary to avoid a type II error, and we included at least five additional participants per group to account for two possible baseline covariates. Values are expressed as mean (SD), except in figures, which include SEM to improve visual clarity. Analysis was performed with SAS statistical software version 9.2 (SAS Institute Inc, Cary, NC).

Results

Ninety women who previously completed weight loss interventions in our laboratory were contacted for this study. Sixty-one responded to these inquiries, and 19 were excluded (owing to initiation of osteoporosis medications, initiation of a rigorous exercise program, cancer diagnosis, initiation of diabetes medications, or refusal to participate; Figure 1). Forty-two postmenopausal women agreed to participate and met criteria for inclusion in this follow-up study. Participants were white (n = 40) and African American (n = 2). Measurements were taken an average of 22 (6) months after the initiation of weight loss. At baseline, there were no significant differences in age, weight, body mass index (BMI), time since menopause, bone, or soft-tissue data between the groups ( ). In both groups of women, 12% to 15% had surgical or drug-induced menopause. For women who refused to participate or could not be contacted, we analyzed a subset (n = 31); their age, BMI, and weight loss did not differ from those included in this study.

Table 1. Baseline and percent change in women who lost weight and either maintained or regained the weight. 

  WL-M group (n = 22) WL-R group (n = 20)
  % Change   % Change
Baseline a 6 mo 2 y Baseline 6 mo 2 y
Age, y 61.3 (5.6)     60.1 (5.2)    
TSM, y 10.5 (7.7)     11.4 (7.3)    
BMI, kg/m2 27.7 (2.6)     28.9 (3.0)    
Body weight, kg 73.1 (7.1) −10.2 (3.2) b −10.3 (4.2) b 75.3 (7.0) −8.2 (3.3) b −2.8 (3.3) b,c
FFST, kg 36.0 (3.3) −3.3 (4.3) b −3.8 (5.5) b 36.4 (3.9) −3.4 (5.5) b −1.9 (6.4)
Fat mass, kg 30.7 (4.8) −18.2 (8.7) b −16.6 (10.5) b 33.0 (5.1) −13.6 (6.7) b −5.4 (6.6) b,c
Trunk fat, kg 13.1 (2.4) −18.2 (14.0) b −19.1 (17.4) b 14.5 (2.5) −14.1 (6.7) b −4.9 (11.5) c
Leg fat, kg 10.8 (1.9) −13.9 (11.1) b −16.9 (13.0) b 11.2 (2.4) −12.0 (7.6) b −2.5 (9.9) c
BMD, g/cm2
Femoral neck 0.86 (0.11) −0.5 (3.1) −2.9 (4.3) b 0.87 (0.09) − 0.1 (3.2) − 2.2 (3.3) b
Trochanter 0.73 (0.11) −4.1 (4.4) b −6.8 (5.7) b 0.75 (0.11) −2.6 (4.7) b −2.5 (6.1) c,d
UD radius 0.31 (0.04) −1.5 (3.9) d −1.0 (4.6) 0.32 (0.05) 0.7 (3.4) e −2.0 (3.9)
1/3 Radius 0.63 (0.09) −1.8 (2.3) b −4.5 (3.3) b 0.64 (0.07) −0.9 (2.9) −1.6 (3.8) c,d
Spine 0.99 (0.09) −3.3 (5.3) b −1.3 (6.4) 0.99 (0.13) −2.9 (4.7) b −2.5 (6.3) d
Total body 1.11 (0.08) −1.1 (1.8) b −1.5 (1.7) b 1.12 (0.08) −0.4 (1.7) −0.5 (1.9) e
BMC, g
Femoral neck 4.40 (0.83) −1.3 (6.2) − 1.4 (5.2) 4.34 (0.43) −1.4 (5.4) −1.5 (6.2)
Trochanter 8.48 (1.82) −2.3 (8.8) −6.0 (9.0) b 8.97 (2.24) 3.5 (8.8) −1.3 (10.7) c
UD radius 1.11 (0.16) −1.3 (9.1) −4.7 (12.4) 1.13 (0.17) 1.7 (12.1) −4.1 (15.7)
1/3 Radius 1.57 (0.21) −2.8 (2.6) b −4.1 (3.2) b 1.53 (0.19) −1.8 (4.3) b −1.3 (5.6) c
Total body 2,276 (271) −1.6 (5.3) −2.7 (5.1) b 2,309 (257) −0.6 (3.9) −1.7 (4.3)

Data are presented as mean (SD). 1.13 (0.17)
Weight loss period refers to 0 to 0.5 y. Baseline to final period refers to 0 to 2 y.
WL-M, weight loss maintainer; WL-R, weight loss regainer; TSM, time since menopause; BMI, body mass index; FFST, fat-free soft tissue; BMD, bone mineral density; UD, ultradistal; BMC, bone mineral content.
a No significant differences among groups were observed for any variable at baseline.
b Differs from baseline (P < 0.05).
c Differs from the WL-M group (P < 0.05).
d P ≤ 0.09.
e P ≤ 0.09 (same period).

Figure 1.

 

Recruitment flow chart. WL-M, weight loss maintainer; WL-R, weight loss regainer.

Dietary Intake

The baseline total calcium intake (diet and supplement) was 948 (352) mg/day, which did not differ significantly between the WL-M group and the WL-R group. In the parent study (0-6 mo), there were equal numbers (n = 13) of women assigned to normal Ca intake in each weight loss group, and the remaining women were assigned to higher Ca intake in the WL-M (n = 9) and WL-R (n = 7) groups. Total calcium intake during the weight loss intervention was 1,275 (406) mg/day in the WL-M group (n = 22) and 1,194 (389) mg/day in the WL-R group (n = 20), which did not differ significantly between the two groups. In addition, total calcium intake after 2 years (1,211 [512] mg/d) also did not differ between the groups. Participants consumed 400 IU/day of vitamin D in their multivitamin throughout the 2-year period. They consumed a small amount in their diet during active weight loss (64 [43] IU/d) and during the nointervention period (88 [84] IU/d), which did not vary significantly between the groups.

Body Weight and Soft Tissue

After the 6-month weight loss protocol, there were no significant differences in weight loss (9.3% [3.5%]) in the WL-R and WL-M groups. However, weight loss differed significantly between the groups for two years ( ). During the post-weight loss period (6 mo to 2 y), the WL-M group lost an average of 0.1 (2.0) kg, whereas the WL-R group gained 4.1 (2.3) kg (P ≤ 0.0001; Figure 2). There were also significant differences between the groups in total, trunk, and leg fat, with greater gain in the WL-R group compared with the WL-M group (P < 0.01; ). FFST decreased after 2 years in all women (−1.2 [2.2] kg or −2.9% [5.6%]) and did not differ significantly between the groups. Weight and fat mass (total, trunk, and leg) were significantly different between the groups at 2 years (P < 0.001), with higher values in the WL-R group compared with the WL-M group.

Table 1. Baseline and percent change in women who lost weight and either maintained or regained the weight. 

  WL-M group (n = 22) WL-R group (n = 20)
  % Change   % Change
Baseline a 6 mo 2 y Baseline 6 mo 2 y
Age, y 61.3 (5.6)     60.1 (5.2)    
TSM, y 10.5 (7.7)     11.4 (7.3)    
BMI, kg/m2 27.7 (2.6)     28.9 (3.0)    
Body weight, kg 73.1 (7.1) −10.2 (3.2) b −10.3 (4.2) b 75.3 (7.0) −8.2 (3.3) b −2.8 (3.3) b,c
FFST, kg 36.0 (3.3) −3.3 (4.3) b −3.8 (5.5) b 36.4 (3.9) −3.4 (5.5) b −1.9 (6.4)
Fat mass, kg 30.7 (4.8) −18.2 (8.7) b −16.6 (10.5) b 33.0 (5.1) −13.6 (6.7) b −5.4 (6.6) b,c
Trunk fat, kg 13.1 (2.4) −18.2 (14.0) b −19.1 (17.4) b 14.5 (2.5) −14.1 (6.7) b −4.9 (11.5) c
Leg fat, kg 10.8 (1.9) −13.9 (11.1) b −16.9 (13.0) b 11.2 (2.4) −12.0 (7.6) b −2.5 (9.9) c
BMD, g/cm2
Femoral neck 0.86 (0.11) −0.5 (3.1) −2.9 (4.3) b 0.87 (0.09) − 0.1 (3.2) − 2.2 (3.3) b
Trochanter 0.73 (0.11) −4.1 (4.4) b −6.8 (5.7) b 0.75 (0.11) −2.6 (4.7) b −2.5 (6.1) c,d
UD radius 0.31 (0.04) −1.5 (3.9) d −1.0 (4.6) 0.32 (0.05) 0.7 (3.4) e −2.0 (3.9)
1/3 Radius 0.63 (0.09) −1.8 (2.3) b −4.5 (3.3) b 0.64 (0.07) −0.9 (2.9) −1.6 (3.8) c,d
Spine 0.99 (0.09) −3.3 (5.3) b −1.3 (6.4) 0.99 (0.13) −2.9 (4.7) b −2.5 (6.3) d
Total body 1.11 (0.08) −1.1 (1.8) b −1.5 (1.7) b 1.12 (0.08) −0.4 (1.7) −0.5 (1.9) e
BMC, g
Femoral neck 4.40 (0.83) −1.3 (6.2) − 1.4 (5.2) 4.34 (0.43) −1.4 (5.4) −1.5 (6.2)
Trochanter 8.48 (1.82) −2.3 (8.8) −6.0 (9.0) b 8.97 (2.24) 3.5 (8.8) −1.3 (10.7) c
UD radius 1.11 (0.16) −1.3 (9.1) −4.7 (12.4) 1.13 (0.17) 1.7 (12.1) −4.1 (15.7)
1/3 Radius 1.57 (0.21) −2.8 (2.6) b −4.1 (3.2) b 1.53 (0.19) −1.8 (4.3) b −1.3 (5.6) c
Total body 2,276 (271) −1.6 (5.3) −2.7 (5.1) b 2,309 (257) −0.6 (3.9) −1.7 (4.3)

Data are presented as mean (SD). 1.13 (0.17)
Weight loss period refers to 0 to 0.5 y. Baseline to final period refers to 0 to 2 y.
WL-M, weight loss maintainer; WL-R, weight loss regainer; TSM, time since menopause; BMI, body mass index; FFST, fat-free soft tissue; BMD, bone mineral density; UD, ultradistal; BMC, bone mineral content.
a No significant differences among groups were observed for any variable at baseline.
b Differs from baseline (P < 0.05).
c Differs from the WL-M group (P < 0.05).
d P ≤ 0.09.
e P ≤ 0.09 (same period).

Table 1. Baseline and percent change in women who lost weight and either maintained or regained the weight. 

  WL-M group (n = 22) WL-R group (n = 20)
  % Change   % Change
Baseline a 6 mo 2 y Baseline 6 mo 2 y
Age, y 61.3 (5.6)     60.1 (5.2)    
TSM, y 10.5 (7.7)     11.4 (7.3)    
BMI, kg/m2 27.7 (2.6)     28.9 (3.0)    
Body weight, kg 73.1 (7.1) −10.2 (3.2) b −10.3 (4.2) b 75.3 (7.0) −8.2 (3.3) b −2.8 (3.3) b,c
FFST, kg 36.0 (3.3) −3.3 (4.3) b −3.8 (5.5) b 36.4 (3.9) −3.4 (5.5) b −1.9 (6.4)
Fat mass, kg 30.7 (4.8) −18.2 (8.7) b −16.6 (10.5) b 33.0 (5.1) −13.6 (6.7) b −5.4 (6.6) b,c
Trunk fat, kg 13.1 (2.4) −18.2 (14.0) b −19.1 (17.4) b 14.5 (2.5) −14.1 (6.7) b −4.9 (11.5) c
Leg fat, kg 10.8 (1.9) −13.9 (11.1) b −16.9 (13.0) b 11.2 (2.4) −12.0 (7.6) b −2.5 (9.9) c
BMD, g/cm2
Femoral neck 0.86 (0.11) −0.5 (3.1) −2.9 (4.3) b 0.87 (0.09) − 0.1 (3.2) − 2.2 (3.3) b
Trochanter 0.73 (0.11) −4.1 (4.4) b −6.8 (5.7) b 0.75 (0.11) −2.6 (4.7) b −2.5 (6.1) c,d
UD radius 0.31 (0.04) −1.5 (3.9) d −1.0 (4.6) 0.32 (0.05) 0.7 (3.4) e −2.0 (3.9)
1/3 Radius 0.63 (0.09) −1.8 (2.3) b −4.5 (3.3) b 0.64 (0.07) −0.9 (2.9) −1.6 (3.8) c,d
Spine 0.99 (0.09) −3.3 (5.3) b −1.3 (6.4) 0.99 (0.13) −2.9 (4.7) b −2.5 (6.3) d
Total body 1.11 (0.08) −1.1 (1.8) b −1.5 (1.7) b 1.12 (0.08) −0.4 (1.7) −0.5 (1.9) e
BMC, g
Femoral neck 4.40 (0.83) −1.3 (6.2) − 1.4 (5.2) 4.34 (0.43) −1.4 (5.4) −1.5 (6.2)
Trochanter 8.48 (1.82) −2.3 (8.8) −6.0 (9.0) b 8.97 (2.24) 3.5 (8.8) −1.3 (10.7) c
UD radius 1.11 (0.16) −1.3 (9.1) −4.7 (12.4) 1.13 (0.17) 1.7 (12.1) −4.1 (15.7)
1/3 Radius 1.57 (0.21) −2.8 (2.6) b −4.1 (3.2) b 1.53 (0.19) −1.8 (4.3) b −1.3 (5.6) c
Total body 2,276 (271) −1.6 (5.3) −2.7 (5.1) b 2,309 (257) −0.6 (3.9) −1.7 (4.3)

Data are presented as mean (SD). 1.13 (0.17)
Weight loss period refers to 0 to 0.5 y. Baseline to final period refers to 0 to 2 y.
WL-M, weight loss maintainer; WL-R, weight loss regainer; TSM, time since menopause; BMI, body mass index; FFST, fat-free soft tissue; BMD, bone mineral density; UD, ultradistal; BMC, bone mineral content.
a No significant differences among groups were observed for any variable at baseline.
b Differs from baseline (P < 0.05).
c Differs from the WL-M group (P < 0.05).
d P ≤ 0.09.
e P ≤ 0.09 (same period).

Figure 2.

 

Weight (kg), fat, and fat-free soft tissue at baseline, at the end of the weight loss intervention (0.5 y), and after 2 years in the weight loss maintainer (WL-M; n = 22) and weight loss regainer (WL-R; n = 20) groups. Data are presented as mean (SEM).
*Repeated-measures analysis of variance differs between the groups, P < 0.05. The only time point that differed between the groups was at 2 years for weight and fat (P < 0.001). Values with different letters are significantly different, P < 0.05. Upper-case and lower-case letters are used to denote WL-R and WL-M, respectively.

BMD and Content and Serum Markers

After 6 months of weight loss, BMD at the trochanter (−3.3% [4.6%]) and spine (−3.1% [5.8%]) decreased in both groups (P ≤ 0.01). In the WL-M group, BMD also decreased at the 1/3 radius and total body ( ). Bone mineral content decreased only at the 1/3 radius for both groups during the 6 months of weight loss. Although there was a trend for greater BMD loss at the UD radius during the weight loss period in the WL-M group compared with the WL-R group, no other sites showed differences between the groups ( ).

Table 1. Baseline and percent change in women who lost weight and either maintained or regained the weight. 

  WL-M group (n = 22) WL-R group (n = 20)
  % Change   % Change
Baseline a 6 mo 2 y Baseline 6 mo 2 y
Age, y 61.3 (5.6)     60.1 (5.2)    
TSM, y 10.5 (7.7)     11.4 (7.3)    
BMI, kg/m2 27.7 (2.6)     28.9 (3.0)    
Body weight, kg 73.1 (7.1) −10.2 (3.2) b −10.3 (4.2) b 75.3 (7.0) −8.2 (3.3) b −2.8 (3.3) b,c
FFST, kg 36.0 (3.3) −3.3 (4.3) b −3.8 (5.5) b 36.4 (3.9) −3.4 (5.5) b −1.9 (6.4)
Fat mass, kg 30.7 (4.8) −18.2 (8.7) b −16.6 (10.5) b 33.0 (5.1) −13.6 (6.7) b −5.4 (6.6) b,c
Trunk fat, kg 13.1 (2.4) −18.2 (14.0) b −19.1 (17.4) b 14.5 (2.5) −14.1 (6.7) b −4.9 (11.5) c
Leg fat, kg 10.8 (1.9) −13.9 (11.1) b −16.9 (13.0) b 11.2 (2.4) −12.0 (7.6) b −2.5 (9.9) c
BMD, g/cm2
Femoral neck 0.86 (0.11) −0.5 (3.1) −2.9 (4.3) b 0.87 (0.09) − 0.1 (3.2) − 2.2 (3.3) b
Trochanter 0.73 (0.11) −4.1 (4.4) b −6.8 (5.7) b 0.75 (0.11) −2.6 (4.7) b −2.5 (6.1) c,d
UD radius 0.31 (0.04) −1.5 (3.9) d −1.0 (4.6) 0.32 (0.05) 0.7 (3.4) e −2.0 (3.9)
1/3 Radius 0.63 (0.09) −1.8 (2.3) b −4.5 (3.3) b 0.64 (0.07) −0.9 (2.9) −1.6 (3.8) c,d
Spine 0.99 (0.09) −3.3 (5.3) b −1.3 (6.4) 0.99 (0.13) −2.9 (4.7) b −2.5 (6.3) d
Total body 1.11 (0.08) −1.1 (1.8) b −1.5 (1.7) b 1.12 (0.08) −0.4 (1.7) −0.5 (1.9) e
BMC, g
Femoral neck 4.40 (0.83) −1.3 (6.2) − 1.4 (5.2) 4.34 (0.43) −1.4 (5.4) −1.5 (6.2)
Trochanter 8.48 (1.82) −2.3 (8.8) −6.0 (9.0) b 8.97 (2.24) 3.5 (8.8) −1.3 (10.7) c
UD radius 1.11 (0.16) −1.3 (9.1) −4.7 (12.4) 1.13 (0.17) 1.7 (12.1) −4.1 (15.7)
1/3 Radius 1.57 (0.21) −2.8 (2.6) b −4.1 (3.2) b 1.53 (0.19) −1.8 (4.3) b −1.3 (5.6) c
Total body 2,276 (271) −1.6 (5.3) −2.7 (5.1) b 2,309 (257) −0.6 (3.9) −1.7 (4.3)

Data are presented as mean (SD). 1.13 (0.17)
Weight loss period refers to 0 to 0.5 y. Baseline to final period refers to 0 to 2 y.
WL-M, weight loss maintainer; WL-R, weight loss regainer; TSM, time since menopause; BMI, body mass index; FFST, fat-free soft tissue; BMD, bone mineral density; UD, ultradistal; BMC, bone mineral content.
a No significant differences among groups were observed for any variable at baseline.
b Differs from baseline (P < 0.05).
c Differs from the WL-M group (P < 0.05).
d P ≤ 0.09.
e P ≤ 0.09 (same period).

Table 1. Baseline and percent change in women who lost weight and either maintained or regained the weight. 

  WL-M group (n = 22) WL-R group (n = 20)
  % Change   % Change
Baseline a 6 mo 2 y Baseline 6 mo 2 y
Age, y 61.3 (5.6)     60.1 (5.2)    
TSM, y 10.5 (7.7)     11.4 (7.3)    
BMI, kg/m2 27.7 (2.6)     28.9 (3.0)    
Body weight, kg 73.1 (7.1) −10.2 (3.2) b −10.3 (4.2) b 75.3 (7.0) −8.2 (3.3) b −2.8 (3.3) b,c
FFST, kg 36.0 (3.3) −3.3 (4.3) b −3.8 (5.5) b 36.4 (3.9) −3.4 (5.5) b −1.9 (6.4)
Fat mass, kg 30.7 (4.8) −18.2 (8.7) b −16.6 (10.5) b 33.0 (5.1) −13.6 (6.7) b −5.4 (6.6) b,c
Trunk fat, kg 13.1 (2.4) −18.2 (14.0) b −19.1 (17.4) b 14.5 (2.5) −14.1 (6.7) b −4.9 (11.5) c
Leg fat, kg 10.8 (1.9) −13.9 (11.1) b −16.9 (13.0) b 11.2 (2.4) −12.0 (7.6) b −2.5 (9.9) c
BMD, g/cm2
Femoral neck 0.86 (0.11) −0.5 (3.1) −2.9 (4.3) b 0.87 (0.09) − 0.1 (3.2) − 2.2 (3.3) b
Trochanter 0.73 (0.11) −4.1 (4.4) b −6.8 (5.7) b 0.75 (0.11) −2.6 (4.7) b −2.5 (6.1) c,d
UD radius 0.31 (0.04) −1.5 (3.9) d −1.0 (4.6) 0.32 (0.05) 0.7 (3.4) e −2.0 (3.9)
1/3 Radius 0.63 (0.09) −1.8 (2.3) b −4.5 (3.3) b 0.64 (0.07) −0.9 (2.9) −1.6 (3.8) c,d
Spine 0.99 (0.09) −3.3 (5.3) b −1.3 (6.4) 0.99 (0.13) −2.9 (4.7) b −2.5 (6.3) d
Total body 1.11 (0.08) −1.1 (1.8) b −1.5 (1.7) b 1.12 (0.08) −0.4 (1.7) −0.5 (1.9) e
BMC, g
Femoral neck 4.40 (0.83) −1.3 (6.2) − 1.4 (5.2) 4.34 (0.43) −1.4 (5.4) −1.5 (6.2)
Trochanter 8.48 (1.82) −2.3 (8.8) −6.0 (9.0) b 8.97 (2.24) 3.5 (8.8) −1.3 (10.7) c
UD radius 1.11 (0.16) −1.3 (9.1) −4.7 (12.4) 1.13 (0.17) 1.7 (12.1) −4.1 (15.7)
1/3 Radius 1.57 (0.21) −2.8 (2.6) b −4.1 (3.2) b 1.53 (0.19) −1.8 (4.3) b −1.3 (5.6) c
Total body 2,276 (271) −1.6 (5.3) −2.7 (5.1) b 2,309 (257) −0.6 (3.9) −1.7 (4.3)

Data are presented as mean (SD). 1.13 (0.17)
Weight loss period refers to 0 to 0.5 y. Baseline to final period refers to 0 to 2 y.
WL-M, weight loss maintainer; WL-R, weight loss regainer; TSM, time since menopause; BMI, body mass index; FFST, fat-free soft tissue; BMD, bone mineral density; UD, ultradistal; BMC, bone mineral content.
a No significant differences among groups were observed for any variable at baseline.
b Differs from baseline (P < 0.05).
c Differs from the WL-M group (P < 0.05).
d P ≤ 0.09.
e P ≤ 0.09 (same period).

During the postintervention period (6 mo to 2 y), there was a further decrease in BMD at the femoral neck in both groups (Figure 3). The trochanter and 1/3 radius BMD continued to decrease during the postintervention period in the WL-M group. Repeated-measures ANOVA showed significantly greater BMD loss across time (2 y) between the groups at the trochanter (P < 0.02) and a trend at the 1/3 radius ( , Figure 3). Across 2 years, BMD decreased significantly at most sites and in both groups (Figure 3). Bone mineral content decreased more at the 1/3 radius and trochanter in the WL-M group than in the WL-R group (P < 0.05) after 2 years ( ).

Table 1. Baseline and percent change in women who lost weight and either maintained or regained the weight. 

  WL-M group (n = 22) WL-R group (n = 20)
  % Change   % Change
Baseline a 6 mo 2 y Baseline 6 mo 2 y
Age, y 61.3 (5.6)     60.1 (5.2)    
TSM, y 10.5 (7.7)     11.4 (7.3)    
BMI, kg/m2 27.7 (2.6)     28.9 (3.0)    
Body weight, kg 73.1 (7.1) −10.2 (3.2) b −10.3 (4.2) b 75.3 (7.0) −8.2 (3.3) b −2.8 (3.3) b,c
FFST, kg 36.0 (3.3) −3.3 (4.3) b −3.8 (5.5) b 36.4 (3.9) −3.4 (5.5) b −1.9 (6.4)
Fat mass, kg 30.7 (4.8) −18.2 (8.7) b −16.6 (10.5) b 33.0 (5.1) −13.6 (6.7) b −5.4 (6.6) b,c
Trunk fat, kg 13.1 (2.4) −18.2 (14.0) b −19.1 (17.4) b 14.5 (2.5) −14.1 (6.7) b −4.9 (11.5) c
Leg fat, kg 10.8 (1.9) −13.9 (11.1) b −16.9 (13.0) b 11.2 (2.4) −12.0 (7.6) b −2.5 (9.9) c
BMD, g/cm2
Femoral neck 0.86 (0.11) −0.5 (3.1) −2.9 (4.3) b 0.87 (0.09) − 0.1 (3.2) − 2.2 (3.3) b
Trochanter 0.73 (0.11) −4.1 (4.4) b −6.8 (5.7) b 0.75 (0.11) −2.6 (4.7) b −2.5 (6.1) c,d
UD radius 0.31 (0.04) −1.5 (3.9) d −1.0 (4.6) 0.32 (0.05) 0.7 (3.4) e −2.0 (3.9)
1/3 Radius 0.63 (0.09) −1.8 (2.3) b −4.5 (3.3) b 0.64 (0.07) −0.9 (2.9) −1.6 (3.8) c,d
Spine 0.99 (0.09) −3.3 (5.3) b −1.3 (6.4) 0.99 (0.13) −2.9 (4.7) b −2.5 (6.3) d
Total body 1.11 (0.08) −1.1 (1.8) b −1.5 (1.7) b 1.12 (0.08) −0.4 (1.7) −0.5 (1.9) e
BMC, g
Femoral neck 4.40 (0.83) −1.3 (6.2) − 1.4 (5.2) 4.34 (0.43) −1.4 (5.4) −1.5 (6.2)
Trochanter 8.48 (1.82) −2.3 (8.8) −6.0 (9.0) b 8.97 (2.24) 3.5 (8.8) −1.3 (10.7) c
UD radius 1.11 (0.16) −1.3 (9.1) −4.7 (12.4) 1.13 (0.17) 1.7 (12.1) −4.1 (15.7)
1/3 Radius 1.57 (0.21) −2.8 (2.6) b −4.1 (3.2) b 1.53 (0.19) −1.8 (4.3) b −1.3 (5.6) c
Total body 2,276 (271) −1.6 (5.3) −2.7 (5.1) b 2,309 (257) −0.6 (3.9) −1.7 (4.3)

Data are presented as mean (SD). 1.13 (0.17)
Weight loss period refers to 0 to 0.5 y. Baseline to final period refers to 0 to 2 y.
WL-M, weight loss maintainer; WL-R, weight loss regainer; TSM, time since menopause; BMI, body mass index; FFST, fat-free soft tissue; BMD, bone mineral density; UD, ultradistal; BMC, bone mineral content.
a No significant differences among groups were observed for any variable at baseline.
b Differs from baseline (P < 0.05).
c Differs from the WL-M group (P < 0.05).
d P ≤ 0.09.
e P ≤ 0.09 (same period).

Table 1. Baseline and percent change in women who lost weight and either maintained or regained the weight. 

  WL-M group (n = 22) WL-R group (n = 20)
  % Change   % Change
Baseline a 6 mo 2 y Baseline 6 mo 2 y
Age, y 61.3 (5.6)     60.1 (5.2)    
TSM, y 10.5 (7.7)     11.4 (7.3)    
BMI, kg/m2 27.7 (2.6)     28.9 (3.0)    
Body weight, kg 73.1 (7.1) −10.2 (3.2) b −10.3 (4.2) b 75.3 (7.0) −8.2 (3.3) b −2.8 (3.3) b,c
FFST, kg 36.0 (3.3) −3.3 (4.3) b −3.8 (5.5) b 36.4 (3.9) −3.4 (5.5) b −1.9 (6.4)
Fat mass, kg 30.7 (4.8) −18.2 (8.7) b −16.6 (10.5) b 33.0 (5.1) −13.6 (6.7) b −5.4 (6.6) b,c
Trunk fat, kg 13.1 (2.4) −18.2 (14.0) b −19.1 (17.4) b 14.5 (2.5) −14.1 (6.7) b −4.9 (11.5) c
Leg fat, kg 10.8 (1.9) −13.9 (11.1) b −16.9 (13.0) b 11.2 (2.4) −12.0 (7.6) b −2.5 (9.9) c
BMD, g/cm2
Femoral neck 0.86 (0.11) −0.5 (3.1) −2.9 (4.3) b 0.87 (0.09) − 0.1 (3.2) − 2.2 (3.3) b
Trochanter 0.73 (0.11) −4.1 (4.4) b −6.8 (5.7) b 0.75 (0.11) −2.6 (4.7) b −2.5 (6.1) c,d
UD radius 0.31 (0.04) −1.5 (3.9) d −1.0 (4.6) 0.32 (0.05) 0.7 (3.4) e −2.0 (3.9)
1/3 Radius 0.63 (0.09) −1.8 (2.3) b −4.5 (3.3) b 0.64 (0.07) −0.9 (2.9) −1.6 (3.8) c,d
Spine 0.99 (0.09) −3.3 (5.3) b −1.3 (6.4) 0.99 (0.13) −2.9 (4.7) b −2.5 (6.3) d
Total body 1.11 (0.08) −1.1 (1.8) b −1.5 (1.7) b 1.12 (0.08) −0.4 (1.7) −0.5 (1.9) e
BMC, g
Femoral neck 4.40 (0.83) −1.3 (6.2) − 1.4 (5.2) 4.34 (0.43) −1.4 (5.4) −1.5 (6.2)
Trochanter 8.48 (1.82) −2.3 (8.8) −6.0 (9.0) b 8.97 (2.24) 3.5 (8.8) −1.3 (10.7) c
UD radius 1.11 (0.16) −1.3 (9.1) −4.7 (12.4) 1.13 (0.17) 1.7 (12.1) −4.1 (15.7)
1/3 Radius 1.57 (0.21) −2.8 (2.6) b −4.1 (3.2) b 1.53 (0.19) −1.8 (4.3) b −1.3 (5.6) c
Total body 2,276 (271) −1.6 (5.3) −2.7 (5.1) b 2,309 (257) −0.6 (3.9) −1.7 (4.3)

Data are presented as mean (SD). 1.13 (0.17)
Weight loss period refers to 0 to 0.5 y. Baseline to final period refers to 0 to 2 y.
WL-M, weight loss maintainer; WL-R, weight loss regainer; TSM, time since menopause; BMI, body mass index; FFST, fat-free soft tissue; BMD, bone mineral density; UD, ultradistal; BMC, bone mineral content.
a No significant differences among groups were observed for any variable at baseline.
b Differs from baseline (P < 0.05).
c Differs from the WL-M group (P < 0.05).
d P ≤ 0.09.
e P ≤ 0.09 (same period).

Figure 3.

 

Bone mineral density (BMD) at baseline, at the end of the weight loss intervention (0.5 y), and on follow-up (2 y) in the weight loss maintainer (WL-M; n = 22) and weight loss regainer (WL-R; n = 20) groups. Data are presented as mean (SEM).
*Repeated-measures analysis of variance differs between the groups (P < 0.02). P < 0.08. There are no significant between-group differences at any time point. Values with different letters are significantly different. Upper-case and lower-case letters are used to denote WL-R and WL-M, respectively. UD, ultradistal.

Bone turnover markers and hormone values did not differ between the groups at baseline in the entire population or subset (see , Supplemental Digital Content 1, http://links.lww.com/MENO/A66). Across the 2-year period, the bone resorption marker serum N-telopeptide of type I collagen increased more in the WL-M group than in the WL-R group (P < 0.05). In addition, serum PTH tended to increase more in the WL-M group than in the WL-R group (P < 0.09). Changes in serum 25(OH)D, estradiol, and osteocalcin did not differ between the WL-M group and the WL-R group.

Table 1. Baseline and percent change in women who lost weight and either maintained or regained the weight. 

  WL-M group (n = 22) WL-R group (n = 20)
  % Change   % Change
Baseline a 6 mo 2 y Baseline 6 mo 2 y
Age, y 61.3 (5.6)     60.1 (5.2)    
TSM, y 10.5 (7.7)     11.4 (7.3)    
BMI, kg/m2 27.7 (2.6)     28.9 (3.0)    
Body weight, kg 73.1 (7.1) −10.2 (3.2) b −10.3 (4.2) b 75.3 (7.0) −8.2 (3.3) b −2.8 (3.3) b,c
FFST, kg 36.0 (3.3) −3.3 (4.3) b −3.8 (5.5) b 36.4 (3.9) −3.4 (5.5) b −1.9 (6.4)
Fat mass, kg 30.7 (4.8) −18.2 (8.7) b −16.6 (10.5) b 33.0 (5.1) −13.6 (6.7) b −5.4 (6.6) b,c
Trunk fat, kg 13.1 (2.4) −18.2 (14.0) b −19.1 (17.4) b 14.5 (2.5) −14.1 (6.7) b −4.9 (11.5) c
Leg fat, kg 10.8 (1.9) −13.9 (11.1) b −16.9 (13.0) b 11.2 (2.4) −12.0 (7.6) b −2.5 (9.9) c
BMD, g/cm2
Femoral neck 0.86 (0.11) −0.5 (3.1) −2.9 (4.3) b 0.87 (0.09) − 0.1 (3.2) − 2.2 (3.3) b
Trochanter 0.73 (0.11) −4.1 (4.4) b −6.8 (5.7) b 0.75 (0.11) −2.6 (4.7) b −2.5 (6.1) c,d
UD radius 0.31 (0.04) −1.5 (3.9) d −1.0 (4.6) 0.32 (0.05) 0.7 (3.4) e −2.0 (3.9)
1/3 Radius 0.63 (0.09) −1.8 (2.3) b −4.5 (3.3) b 0.64 (0.07) −0.9 (2.9) −1.6 (3.8) c,d
Spine 0.99 (0.09) −3.3 (5.3) b −1.3 (6.4) 0.99 (0.13) −2.9 (4.7) b −2.5 (6.3) d
Total body 1.11 (0.08) −1.1 (1.8) b −1.5 (1.7) b 1.12 (0.08) −0.4 (1.7) −0.5 (1.9) e
BMC, g
Femoral neck 4.40 (0.83) −1.3 (6.2) − 1.4 (5.2) 4.34 (0.43) −1.4 (5.4) −1.5 (6.2)
Trochanter 8.48 (1.82) −2.3 (8.8) −6.0 (9.0) b 8.97 (2.24) 3.5 (8.8) −1.3 (10.7) c
UD radius 1.11 (0.16) −1.3 (9.1) −4.7 (12.4) 1.13 (0.17) 1.7 (12.1) −4.1 (15.7)
1/3 Radius 1.57 (0.21) −2.8 (2.6) b −4.1 (3.2) b 1.53 (0.19) −1.8 (4.3) b −1.3 (5.6) c
Total body 2,276 (271) −1.6 (5.3) −2.7 (5.1) b 2,309 (257) −0.6 (3.9) −1.7 (4.3)

Data are presented as mean (SD). 1.13 (0.17)
Weight loss period refers to 0 to 0.5 y. Baseline to final period refers to 0 to 2 y.
WL-M, weight loss maintainer; WL-R, weight loss regainer; TSM, time since menopause; BMI, body mass index; FFST, fat-free soft tissue; BMD, bone mineral density; UD, ultradistal; BMC, bone mineral content.
a No significant differences among groups were observed for any variable at baseline.
b Differs from baseline (P < 0.05).
c Differs from the WL-M group (P < 0.05).
d P ≤ 0.09.
e P ≤ 0.09 (same period).

Predictors of Change in BMD for 2 Years

To determine how age and soft tissue influence BMD, we examined whether leg and trunk fat or FFST was important in predicting the relationship using multiple regression analyses ( ). Age and body composition (leg or trunk fat or FFST) served as explanatory variables for each of the dependent variables. As expected, age did not have a significant independent association with bone loss because there was a relatively narrow age range (53-72 y; ). Changes in trochanter BMD were largely explained by changes in leg fat (P < 0.05) and tended to be explained by FFST (P < 0.07). Similarly, leg fat tended to explain changes in total BMD (P < 0.08).

Table 2. Multiple regression model of the relative contribution of age and change in body composition to change in BMD for all women for 2 years (N = 42). 

Variable a Explanatory variable β coefficient P Model R 2 (%)
Trochanter BMD, g/cm2 Fat-free soft tissue 0.3250 0.066 19.5
Leg fat 0.3370 0.043
Age −0.0511 0.749
Trunk fat 0.0072 0.998
Total BMD, g/cm2 Fat-free soft tissue −0.206 0.558 14.9
Leg fat −0.302 0.073
Age 0.063 0.808
Trunk fat 0.058 0.836

BMD, bone mineral density.
a Variables without significant findings or trends are not shown (femoral neck, total spine, ultradistal radius, and 1/3 radius).

Table 2. Multiple regression model of the relative contribution of age and change in body composition to change in BMD for all women for 2 years (N = 42). 

Variable a Explanatory variable β coefficient P Model R 2 (%)
Trochanter BMD, g/cm2 Fat-free soft tissue 0.3250 0.066 19.5
Leg fat 0.3370 0.043
Age −0.0511 0.749
Trunk fat 0.0072 0.998
Total BMD, g/cm2 Fat-free soft tissue −0.206 0.558 14.9
Leg fat −0.302 0.073
Age 0.063 0.808
Trunk fat 0.058 0.836

BMD, bone mineral density.
a Variables without significant findings or trends are not shown (femoral neck, total spine, ultradistal radius, and 1/3 radius).

Discussion

It is well established that weight reduction leads to bone loss.[19] This study was designed to determine whether bone loss continues differently between women who maintain lost weight and women who regain lost weight. We show that overweight and obese postmenopausal women who experience approximately 10% weight reduction and regain approximately 70% of the weight across 18 months have attenuated trochanter and 1/3 radius BMD loss compared with those who maintain a reduced body weight. In women who regain weight, the bone lost during weight reduction is permanent; however, at 2 years, it does not exceed the 0.5% to 1% rate of annual BMD loss expected (depending on the site) because of normal aging.[20-25] These findings suggest that only those women who undergo short-term weight reduction and maintain the lost weight for 2 years continue to lose more BMD at several sites than those who regain the weight.

A few previous studies have addressed the influence of weight loss and weight regain on site-specific BMD.[14-17] The results of these studies have been contradictory, possibly owing to mixed sexes, younger ages of the participants, or shorter study designs.[14-16] In one study, premenopausal women were examined during a 3-month very-low-energy diet (13.2-kg loss), followed by 9 months of randomized controlled walking, and then followed for 2 years after a 62% weight regain.[15] Fogelholm et al[15] reported reduced lumbar spine and femoral neck BMD across 2 years for the entire group, but neither site correlated with weight change. Avenell et al[14] studied BMD in 16 postmenopausal women for 6 months of weight loss followed by 6 months of complete weight regain, and they found greater loss of BMD at the lumbar spine (but not at the femoral neck) than weight-stable women.[14] In another study, 16 frail obese older adults were followed up at 30 months after a 1-year weight loss trial. Their weight remained below baseline and their hip BMD decreased, but there no change in lumbar spine and whole-body BMD.[17] In this same study, physical performance and metabolic profile remained improved after 30 months.[17] In one other study, 23 postmenopausal women were examined at 1 year after 6 months of 5% weight loss.[16] The decrease in lumbar spine and hip BMD attributed to weight loss showed no further decrease during 1 year of weight regain (93% fat mass gain). It was concluded that bone did not recover with weight regain. However, the absence of "bone recovery" is less surprising because it would not be expected with fat mass gain[16] and, in fact, BMD loss would be expected because of aging. Our findings show that not only is there no bone recovery with weight regain but also that BMD loss continues or begins at some bone sites. For example, there was no femoral neck BMD loss after 6 months, but there was a significant 2% loss after 2 years. This delayed response to weight loss may be attributed to the bone remodeling transient that may take up to 2 years to complete.[26] Annual bone loss in weight-stable postmenopausal women reaches up to 1% per year,[20-25] similar to women in the current trial who regained their weight (loss at the femoral neck, −1.1% per year; trochanter, −1.3% per year; UD radius, −1.0% per year). In addition, women who successfully maintained a lower body weight for 2 years (WL-M group) showed an even higher annual BMD loss at the trochanter (~3.3% per year) and 1/3 radius (−2.5% per year). There is also elevated bone resorption at 2 years for women who maintained weight loss compared with those who regained body weight; this is consistent with findings of higher bone resorption at 9 months after a short-term (3 mo) weight loss.[27] These findings clarify that bone loss is permanent and continues at a faster rate for at least 2 years for those who do not regain weight. In addition, although the current study observed only one weight loss cycle, bone loss would be expected to be greater with subsequent weight cycling, as shown in rodents.[12] Furthermore, retrospective studies show that multiple episodes of weight loss and regain (weight cycle) increase fracture risk at some sites,[10,15,28,29] suggesting that, even with a normal annual rate of bone loss observed in the "regain" group for 2 years, bone quality may be compromised. It is possible that bone loss during the post-weight loss period is delayed because of the bone remodeling transient or because of systemic factors that were altered by lowering body weight,[19,26] yet some anatomical sites showed faster, rather than slower, bone loss during this post-weight loss period.

The current study demonstrates that loss of FFST and leg fat is a predictor of bone loss, whereas there was no relationship with trunk fat, which represents a site with greater visceral fat. One recent 3-month weight loss study in young men and women[30] examined how soft-tissue compartments explain BMD loss with and without 6 months of weight regain. The authors concluded that changes in soft-tissue composition had little contribution to changes in BMD with weight loss.[30] However, there was no bone loss with weight loss in these participants, possibly owing to the short-term intervention and/or the young age of the participants[19]; thus, how bone loss is regulated by soft-tissue changes could not be determined. Our results are encouraging because they suggest that fat loss in a predominantly visceral region is not associated with bone loss. Nevertheless, this hypothesis using DXA technology should be confirmed using magnetic resonance imaging and/or quantitative CT to distinguish between different fat depots. Furthermore, it is possible that loss of FFST is exacerbated with each weight loss period,[31] especially in older individuals[32]; this at least partially explains the lower BMD found in weight cyclers.

This study is limited in its interpretation because it is a case-control design rather than a randomized controlled trial, such that women in the two groups were self-selected. In addition, BMD measurement errors are a concern in the obese population owing to excess and homogeneity of fat tissue surrounding bones[33-36] and/or changes in soft tissue with weight reduction. However, we are less concerned about this potential error for a few reasons. First, the results show bone changes at both central and peripheral bone sites that have more and less adiposity, respectively. In addition, adipose tissue change in this moderate weight loss/regain study is less than in studies showing bone measurement errors.[33,34] For example, it has been found that 6 kg or more of fat layering on the region being measured (spine or hip) will artificially increase BMD, but the error was not found using smaller amounts of fat.[37] In the current study, total body fat gain in the weight regain group was only 2.8 kg and, therefore, was well below the threshold where error would be expected; the BMD loss during weight stability (0.5-2 y) in the WL-M group cannot be attributed to changes in fat tissue. In addition, the absence of a control weight maintenance group is also a limitation; however, age-related bone loss has been extensively studied in the literature[20-25] and thus is a smaller concern.

One strength of this study is that participants were measured by the same certified radiology technician using identical instrumentation across 2 years for all three measurements. Also, although participants had different calcium supplementation assignments during the 5-month weight loss, intake was at or above the recommended level in all individuals, there was a relatively even distribution of both levels of calcium between the groups, and both groups had similar calcium intake during months 6 to 24. It is also possible that this data set is biased because it excludes certain women who were not eligible for follow-up (ie, five women were excluded owing to initiation of osteoporosis medications, and nine women were excluded because they were not interested). However, it was encouraging to note that nearly all women contacted agreed to participate (if they met the inclusion criteria) and that those who we were not contacted or did not participate had age, BMI, and weight loss similar to those included in the study. One further limitation is that we did not monitor physical activity during months 6 to 24 and depended on participants to remember whether there were any extreme changes in physical activity (the reason for the exclusion of one woman during screening). It would be expected that those who maintained their body weight (vs regainers) would have been more physically active to maintain their lower weight and that this would have a beneficial effect on bone, yet BMD loss was greater or similar in the group that successfully maintained weight loss.

Conclusions

This study shows that weight reduction-induced bone loss that is apparent immediately after weight loss either continues or first begins at the trochanter, femoral neck, and radius in postmenopausal women. Weight regain does not result in recovery of bone, but it prevents greater loss at the trochanter and 1/3 radius compared with reduced-obese women. Even after weight loss, about 50% of women in the WL-M group were still overweight. Thus, weight loss would be recommended for these individuals, who typically would not be considered at risk for osteoporosis based on their overweight status. There is concern that repeated dieting would enhance bone loss and osteoporosis risk in this population compared with obese women who have been weight-stable, possibly owing to poor bone quality,[38,39] but specific studies have not been conducted.

Hence, questions about weight history should be considered when evaluating risk of osteoporosis. Current recommendations appropriately encourage weight loss in overweight individuals to reduce the risk of comorbidities. Until future prospective studies have addressed how to prevent bone loss after a successful weight reduction, therapies that have been shown toa meliorate bone loss during weight reduction—such as adequate calcium and vitamin D, higher protein intake, and increased bone-loading exercise—should also be encouraged after weight stabilizes. Whether BMD changes in cortical or trabecular bone affect geometry after weight loss remains an important question in the prevention of fracture risk.

References

  1. Riedt CS, Cifuentes M, Stahl T, Chowdhury HA, Schlussel Y, Shapses SA. Overweight postmenopausal women lose bone with moderate weight reduction and 1 g/day calcium intake. J Bone Miner Res 2005; 20:455-463.

  2. Sukumar D, Ambia-Sobhan H, Zurfluh R, et al. Areal and volumetric bone mineral density and geometry at two levels of protein intake during caloric restriction: a randomized, controlled trial. J Bone Miner Res 2011;26:1339-1348.

  3. Villareal DT, Shah K, Banks MR, Sinacore DR, Klein S. Effect of weight loss and exercise therapy on bone metabolism and mass in obese older adults: a one-year randomized controlled trial. J Clin Endocrinol Metab 2008;93:2181-2187.

  4. Gozansky WS, Van Pelt RE, Jankowski CM, Schwartz RS, Kohrt WM. Protection of bone mass by estrogens and raloxifene during exerciseinduced weight Loss. J Clin Endocrinol Metab 2005;90:52-59.

  5. Riedt CS, Schlussel Y, von Thun N, et al. Premenopausal overweight women do not lose bone during moderate weight loss with adequate or higher calcium intake. Am J Clin Nutr 2007;85:972-980.

  6. Shapses SA, Von Thun NL, Heymsfield SB, et al. Bone turnover and density in obese premenopausal women during moderate weight loss and calcium supplementation. J Bone Miner Res 2001;16:1329-1336.

  7. Redman LM, Rood J, Anton SD, Champagne C, Smith SR, Ravussin E. Calorie restriction and bone health in young, overweight individuals. Arch Intern Med 2008;168:1859-1866.

  8. Ensrud KE, Fullman RL, Barrett-Connor E, et al. Voluntary weight reduction in older men increases hip bone loss: the Osteoporotic Fractures in Men Study. J Clin Endocrinol Metab 2005;90:1998-2004.

  9. Ensrud KE, Ewing SK, Stone KL, Cauley JA, Bowman PJ, Cummings SR. Intentional and unintentional weight loss increase bone loss and hip fracture risk in older women. J Am Geriatr Soc 2003;51:1740-1747.

  10. Meyer HE, Tverdal A, Selmer R. Weight variability, weight change and the incidence of hip fracture: a prospective study of 39,000 middle-aged Norwegians. Osteoporos Int 1998;8:373-378.

  11. Beavers KM, Lyles MF, Davis CC, Wang X, Beavers DP, Nicklas BJ. Is lost lean mass from intentional weight loss recovered during weight regain in postmenopausal women? Am J Clin Nutr 2011;94:767-774.

  12. Bogden JD, Kemp FW, Huang AE, et al. Bone mineral density and content during weight cycling in female rats: effects of dietary amylaseresistant starch. Nutr Metab (Lond) 2008;5:34.

  13. Bacon L, Stern JS, Keim NL, Van Loan MD. Low bone mass in premenopausal chronic dieting obese women. Eur J Clin Nutr 2004; 58:966-971.

  14. Avenell A, Richmond PR, Lean ME, Reid DM. Bone loss associated with a high fibre weight reduction diet in postmenopausal women. Eur J Clin Nutr 1994;48:561-566.

  15. Fogelholm GM, Sievanen HT, Kukkonen-Harjula TK, Pasanen ME. Bone mineral density during reduction, maintenance and regain of body weight in premenopausal, obese women. Osteoporos Int 2001;12:199-206.

  16. Villalon KL, Gozansky WS, Van Pelt RE, et al. A losing battle: weight regain does not restore weight lossYinduced bone loss in postmenopausal women. Obesity (Silver Spring) 2011;19:2345-2350.

  17. Waters DL, Vawter R, Qualls C, Chode S, Armamento-Villareal R, Villareal DT. Long-term maintenance of weight loss after lifestyle intervention in frail, obese older adults. J Nutr Health Aging 2013; 17:3-7.

  18. Ricci TA, Heymsfield SB, Pierson RN Jr, Stahl T, Chowdhury HA, Shapses SA. Moderate energy restriction increases bone resorption in obese postmenopausal women. Am J Clin Nutr 2001;73:347-352.

  19. Shapses SA, Sukumar D. Bone metabolism in obesity and weight loss. Annu Rev Nutr 2012;32:287-309.

  20. Makovey J, Naganathan V, Seibel M, Sambrook P. Gender differences in plasma ghrelin and its relations to body composition and boneVan opposite-sex twin study. Clin Endocrinol (Oxf) 2007;66:530-537.

  21. Sirola J, Kroger H, Honkanen R, et al. Factors affecting bone loss around menopause in women without HRT: a prospective study. Maturitas 2003;45:159-167.

  22. Nguyen TV, Sambrook PN, Eisman JA. Bone loss, physical activity, and weight change in elderly women: the Dubbo Osteoporosis Epidemiology Study. J Bone Miner Res 1998;13:1458-1467.

  23. Young R, May H, Murphy S, Grey C, Compston JE. Rates of bone loss in peri- and postmenopausal women: a 4 year, prospective, population-based study. Clin Sci (Lond) 1996;91:307-312.

  24. Sornay-Rendu E, Munoz F, Duboeuf F, Delmas PD. Rate of forearm bone loss is associated with an increased risk of fracture independently of bone mass in postmenopausal women: the OFELY study. J Bone Miner Res 2005;20:1929-1935.

  25. Daly RM, Ahlborg HG, Ringsberg K, Gardsell P, Sernbo I, Karlsson MK. Association between changes in habitual physical activity and changes in bone density, muscle strength, and functional performance in elderly men and women. J Am Geriatr Soc 2008;56:2252-2260.

  26. Heaney RP. The bone-remodeling transient: implications for the interpretation of clinical studies of bone mass change. J Bone Miner Res 1994;9:1515-1523.

  27. Hinton PS, LeCheminant JD, Smith BK, Rector RS, Donnelly JE. Weight loss-induced alterations in serum markers of bone turnover persist during weight maintenance in obese men and women. J Am Coll Nutr 2009; 28:565-573.

  28. Sogaard AJ, Meyer HE, Tonstad S, Haheim LL, Holme I. Weight cycling and risk of forearm fractures: a 28-year follow-up of men in the Oslo Study. Am J Epidemiol 2008;167:1005-1013.

  29. Gallagher KI, Jakicic JM, Kiel DP, Page ML, Ferguson ES, Marcus BH. Impact of weight-cycling history on bone density in obese women. Obes Res 2002;10:896-902.

  30. Bosy-Westphal A, Later W, Schautz B, et al. Impact of intra- and extraosseous soft tissue composition on changes in bone mineral density with weight loss and regain. Obesity (Silver Spring) 2011;19:1503-1510.

  31. Lee JS, Visser M, Tylavsky FA, et al. Weight loss and regain and effects on body composition: the Health, Aging, and Body Composition Study. J Gerontol A Biol Sci Med Sci 2010;65:78-83.

  32. Taaffe DR, Cauley JA, Danielson M, et al. Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the Health, Aging, and Body Composition Study. J Bone Miner Res 2001;16:1343-1352.

  33. Tothill P. Dual-energy x-ray absorptiometry measurements of total-body bone mineral during weight change. J Clin Densitom 2005;8:31-38.

  34. Bolotin HH. Analytic and quantitative exposition of patient-specific systematic inaccuracies inherent in planar DXA-derived in vivo BMD measurements. Med Phys 1998;25:139-151.

  35. Blake GM, Fogelman I. How important are BMD accuracy errors for the clinical interpretation of DXA scans? J Bone Miner Res 2008;23: 457-462.

  36. Svendsen OL, Hassager C, Skodt V, Christiansen C. Impact of soft tissue on in vivo accuracy of bone mineral measurements in the spine, hip, and forearm: a human cadaver study. J Bone Miner Res 1995;10: 868-873.

  37. Yu EW, Thomas BJ, Brown JK, Finkelstein JS. Simulated increases in body fat and errors in bone mineral density measurements by DXA and QCT. J Bone Miner Res 2012;27:119-124.

  38. Premaor MO, Pilbrow L, Tonkin C, Parker RA, Compston J. Obesity and fractures in postmenopausal women. J Bone Miner Res 2010;25:292-297.

  39. Sukumar D, Schlussel Y, Riedt CS, Gordon C, Stahl T, Shapses SA. Obesity alters cortical and trabecular bone density and geometry in women. Osteoporos Int 2011;22:635-645.