Two-Year Changes in Bone Density After Roux-en-Y Gastric Bypass Surgery

Elaine W Yu; Mary L Bouxsein; Melissa S Putman; Elizabeth L Monis; Adam E Roy; Janey S A Pratt; W Scott Butsch; Joel S Finkelstein

doi:10.1210/jc.2014-4341

. 2015 Apr 1;100(4):1452–1459. doi: 10.1210/jc.2014-4341

Two-Year Changes in Bone Density After Roux-en-Y Gastric Bypass Surgery

Elaine W Yu ^1,^*, Mary L Bouxsein ¹, Melissa S Putman ¹, Elizabeth L Monis ¹, Adam E Roy ¹, Janey S A Pratt ², W Scott Butsch ², Joel S Finkelstein ¹

PMCID: PMC4399296 PMID: 25646793

Abstract

Context:

Bariatric surgery is increasingly popular but may lead to metabolic bone disease.

Objective:

The objective was to determine the rate of bone loss in the 24 months after Roux-en-Y gastric bypass.

Design and Setting:

This was a prospective cohort study conducted at an academic medical center.

Participants:

The participants were adults with severe obesity, including 30 adults undergoing gastric bypass and 20 nonsurgical controls.

Outcomes:

We measured bone mineral density (BMD) at the lumbar spine and proximal femur by quantitative computed tomography (QCT) and dual-energy x-ray absorptiometry at 0, 12, and 24 months. BMD and bone microarchitecture were also assessed by high-resolution peripheral QCT, and estimated bone strength was calculated using microfinite element analysis.

Results:

Weight loss plateaued 6 months after gastric bypass but remained greater than controls at 24 months (−37 ± 3 vs −5 ± 3 kg [ mean ± SEM]; P < .001). At 24 months, BMD was 5–7% lower at the spine and 6–10% lower at the hip in subjects who underwent gastric bypass compared with nonsurgical controls, as assessed by QCT and dual-energy x-ray absorptiometry (P < .001 for all). Despite significant bone loss, average T-scores remained in the normal range 24 months after gastric bypass. Cortical and trabecular BMD and microarchitecture at the distal radius and tibia deteriorated in the gastric bypass group throughout the 24 months, such that estimated bone strength was 9% lower than controls. The decline in BMD persisted beyond the first year, with rates of bone loss exceeding controls throughout the second year at all skeletal sites. Mean serum calcium, 25(OH)-vitamin D, and PTH were maintained within the normal range in both groups.

Conclusions:

Substantial bone loss occurs throughout the 24 months after gastric bypass despite weight stability in the second year. Although the benefits of gastric bypass surgery are well established, the potential for adverse effects on skeletal integrity remains an important concern.

Although overall rates of obesity have recently plateaued, the prevalence of severe obesity has increased by 70% over the past decade (1). Bariatric surgery is a highly effective treatment for severe obesity, with Roux-en-Y gastric bypass surgery being the most common form of bariatric surgery in the United States and worldwide (2). Postoperative mortality rates are approximately 0.3%, on par with other elective surgeries such as hip replacements, and patients experience dramatic improvements in obesity-related comorbidities such as type 2 diabetes and cardiovascular disease (3). However, metabolic bone disease may be an important unintended consequence of this surgery (4).

Studies indicate that gastric bypass leads to acute bone loss in the first year after surgery (5–10). Although weight loss typically plateaus in the first year after surgery, there are hints that accelerated bone loss may continue beyond this time. Unfortunately, little prospective data exist to document the full duration and magnitude of bone loss after gastric bypass. Continued bone loss over multiple years might increase skeletal fragility and ultimately the risk of fracture in patients who have had gastric bypass surgery.

We previously reported 12-month changes in bone density in a cohort of patients who had undergone gastric bypass and in a well-matched group of nonsurgical obese controls (5). To test the hypothesis that gastric bypass leads to continued bone loss in the subsequent year, we prospectively extended our original study to a total of 24 months. In addition to dual-energy x-ray absorptiometry (DXA) measurements, we assessed bone changes at the spine and hip using quantitative computed tomography (QCT) to mitigate potential imaging artifacts in the setting of obesity and substantial weight loss (11). We also assessed longitudinal changes in bone microarchitecture and estimated bone strength by high-resolution peripheral QCT (HR-pQCT).

Subjects and Methods

Study subjects and protocol

We recruited 50 obese adults from the Massachusetts General Hospital Weight Center and the surrounding community, including 30 subjects undergoing Roux-en-Y gastric bypass surgery and 20 nonsurgical obese controls. Controls were recruited to be of similar age, sex, and weight as the surgical group. Details of the original recruitment have been previously published (5). In brief, subjects were excluded if they had a history of bone-modifying disorders, if they used bone-active medications, or if their weight exceeded the weight limitations of the DXA and CT scanners (eg, 204 kg). Subjects had study visits at baseline (for the surgical group, within 6 wk before gastric bypass) and at months 6, 12, and 24. Forty-six subjects completed the original 12-month study and were eligible for the extension study. The study was approved by the Institutional Review Board at Massachusetts General Hospital, and all subjects provided written informed consent. The study was listed on clinicaltrials.gov (NCT01098942).

DXA bone density

Areal bone mineral density (aBMD; g/cm²) was measured by DXA (QDR Discovery; Hologic, Inc) in array mode at the lumbar spine (L1–L4) and proximal hip at months 0, 6, 12, and 24. The standard procedure for DXA acquisition at our facility includes manual retraction of pannus overlying the proximal femur during hip measurements. Total hip and averaged L1–L4 spine measurements are reported.

QCT bone density

Volumetric BMD (vBMD; mg/cm³) was assessed by QCT (General Electric LightSpeed Pro CT scanner; General Electric Healthcare) at the lumbar spine (L1–L2) and proximal femur at months 0, 12, and 24. QCT scans were performed with helical acquisition, 2.5- mm slice thickness, QCTPro calibration phantom, and the following settings: L1–L2 vertebrae (120 kvP, 100 mA), proximal femur (120 kvP, 200 mA). Analysis of total (including both cortical and trabecular compartments) and trabecular vBMD was performed with QCTPro software (Mindways Software, Inc) as previously described (5).

HR-pQCT bone density and microarchitecture

vBMD and microarchitecture of the distal radius and tibia were assessed at months 0, 12, and 24 using HR-pQCT (XtremeCT; Scanco Medical AG) as previously described (12). Quality control was maintained with daily scanning of the manufacturer's phantom, as well as visual inspection of each HR-pQCT scan by an investigator experienced in this technology. The standard analysis program (Scanco software version V6.0) was used to calculate cortical and trabecular geometry, density, and microarchitecture. To characterize cortical microarchitecture in greater detail, HR-pQCT images were processed by a semiautomated cortical bone segmentation technique (13). After image segmentation, measures were obtained for cortical geometry, density, and porosity. Linear microfinite element analysis was used to estimate failure load (a measure of bone strength) in response to simulated uniaxial compression (14).

Bionutrition measurements

Height was measured in triplicate using a wall-mounted stadiometer (Harpenden; Seritex, Inc). Weight was measured using a digital scale (Tanita BWB-800; Tanita Corporation of America, Inc). Assessments of leisure and occupational physical activity (hours/week) were performed using the modifiable activity questionnaire (15). As is standard practice at our institution, subjects undergoing gastric bypass were counseled to have an intake of 1200–1500 mg/d of calcium and 3000 IU/d of vitamin D through a combination of diet and supplements.

Laboratory tests

Fasting morning serum was collected at each visit. Serum collagen type 1 cross-linked C-telopeptide (CTX) was measured by electrochemiluminescence immunoassay (Roche Diagnostics) with intra- and interassay coefficients of variation of 2 and 3%, respectively. Serum levels of procollagen type 1 N-terminal propeptide (PINP) were measured by RIA (Orion Diagnostica), with intra- and interassay coefficients of variation of approximately 4 and 6%, respectively. We also measured calcium, 25(OH)-vitamin D (immunochemiluminometric assay, Liaison; DiaSorin), and intact PTH (electrochemiluminescence immunoassay; Roche Diagnostics).

Statistical analysis

Baseline characteristics were compared between groups using independent t tests or Fisher's exact tests. Longitudinal values are reported as mean ± SEM unless otherwise noted. A longitudinal general linear mixed effects model (SAS PROC MIXED) with a compound symmetry covariance structure was used to compare mean percentage change in outcomes over the 24-month study between gastric bypass and control groups. The subject-specific intercept was considered a random effect, and time, group, and time by group interaction were considered fixed effects. In addition, the mean percentage change from months 12 to 24 was compared between gastric bypass and control groups using independent t tests to determine more specifically whether there were continued differences in the rate of BMD decline between groups during the second year. Predictors of bone loss within the surgical group were assessed using Pearson's correlations. All analyses were performed using SAS 9.2 software (SAS Institute Inc). P values < .05 were considered significant.

Results

Baseline characteristics

At baseline, groups were well-matched for age, gender, weight, and bionutritional measures (Table 1). There were no significant differences between groups in baseline CTX or PINP; spine or hip BMD; or BMD or microarchitectural measures at the radius or tibia (see Supplemental Tables 1 and 2). Of the 46 subjects who completed the original study, 76% of the surgical subjects (n = 22) and 65% of the nonsurgical controls (n = 11) completed the 24-month extension visits. Reasons for early dropout included moving away and/or loss of interest (n = 9) and interval development of medical conditions rendering them ineligible (n = 4). The baseline characteristics and 12-month changes of the subjects who dropped out were similar to the whole cohort.

Table 1.

Clinical Characteristics and Metabolic Bone Labs in Gastric Bypass and Control Groups at Baseline and Over 24 Months

Months	0	6	12	24
No. of patients
Gastric bypass	30	29	29	22
Controls	20	18	18	11
Age, y
Gastric bypass	47 ± 14
Controls	47 ± 16
Premenopausal women/postmenopausal women/men, %
Gastric bypass	53/33/13
Controls	60/25/15
Weight, kg
Gastric bypass	121 ± 16	91 ± 13^a	82 ± 14^a	86 ± 14^a
Controls	122 ± 22	120 ± 22	121 ± 24	112 ± 21
BMI, kg/m²
Gastric bypass	45 ± 6	34 ± 5^a	32 ± 5^a	32 ± 5^a
Controls	45 ± 6	45 ± 7	45 ± 7	42 ± 6
Physical activity, h/wk
Gastric bypass	19 ± 19	27 ± 29	23 ± 19	19 ± 14
Controls	15 ± 13	14 ± 12	21 ± 21	9 ± 7
Serum calcium, mg/dL
Gastric bypass	9.5 ± 0.4	9.5 ± 0.3	9.3 ± 0.4	9.3 ± 0.3
Controls	9.4 ± 0.6	9.3 ± 0.4	9.3 ± 0.3	9.2 ± 0.2
Serum 25(OH)-vitamin D, ng/mL
Gastric bypass	28 ± 11	29 ± 11	31 ± 10	29 ± 10
Controls	24 ± 10	30 ± 14^a	27 ± 12	22 ± 10
Serum PTH, pg/mL
Gastric bypass	43 ± 22	42 ± 16	43 ± 16	54 ± 27^a
Controls	48 ± 25	46 ± 21	46 ± 19	49 ± 16
Serum CTX, ng/mL
Gastric bypass	0.25 ± 0.12	0.74 ± 0.28^a	0.70 ± 0.28^a	0.61 ± 0.28^a
Controls	0.29 ± 0.14	0.27 ± 0.11	0.28 ± 0.13	0.29 ± 0.18
Serum PINP, μg/mL
Gastric bypass	37.3 ± 15.8	65.7 ± 28.6^a	65.8 ± 36.4^a	62.1 ± 30.0^a
Controls	41.3 ± 21.1	37.2 ± 18.6	39.1 ± 17.8	37.0 ± 13.5

Open in a new tab

Abbreviation: BMI, body mass index. Data are presented as mean ± SD.

^{^a}

P value < .05 for difference in percentage change between gastric bypass and control groups in longitudinal mixed models.

Weight loss

Mean weight loss in the group that underwent gastric bypass surgery was largely achieved in the first 6 months after surgery and plateaued at −37 ± 3 kg by 24 months (Figure 1). By comparison, mean weight loss in the control group was −5 ± 3 kg at 24 months (P < .001 vs gastric bypass group). By 24 months, body mass index was lower in the gastric bypass group than in controls (32 ± 5 vs 42 ± 6 kg/m²; P < .001), although still within the obese range.

Figure 1. — Mean ± SEM weight (kg) in gastric bypass and control groups over 24 months.

*, P value < .001 for the comparison of gastric bypass vs control.

Changes in spine and total hip BMD

In the group that underwent gastric bypass surgery, spine BMD declined progressively throughout the 24-month study, whereas it was relatively constant in the control group (Figure 2, A and B). Compared with controls, spine BMD was 6% lower by DXA and 5% lower by QCT in the gastric bypass group at 24 months (P < .001 for both). Furthermore, the rate of spine BMD decline from months 12 to 24 was greater in the gastric bypass group than in controls, whether assessed by DXA (−2.2 ± 0.6 vs 1.3 ± 1.2%; P = .009) or by QCT (−1.7 ± 0.8 vs 1.1 ± 1.0%; P = .045). Trabecular vBMD at the spine in the gastric bypass group was significantly lower than controls by 24 months (P < .001; Figure 2C). Despite the significant bone loss, the average DXA spine T-score in the gastric bypass group remained in the normal range at 24 months (0.1 ± 1.3).

Figure 2. — Mean ± SEM percentage change in spine and hip BMD in gastric bypass (solid line) and control groups (dotted line) over 24 months.

Spine aBMD by DXA (A), total spine vBMD by QCT (B), trabecular spine vBMD by QCT (C), total hip aBMD by DXA (D), total hip vBMD by QCT (E), and trabecular hip vBMD by QCT (F) are shown in the gastric bypass group relative to controls. P value is for the overall comparison of gastric bypass vs controls over 24 months. Rates of change are reported from month 12 to 24 for gastric bypass and controls. *, P value < .05 for the comparison of gastric bypass vs control specifically from 12 to 24 months.

Total hip BMD also declined significantly more in the gastric bypass group than controls, such that BMD was 10% lower by DXA (P < .001) and 7% lower by QCT (P = .002) at 24 months (Figure 2, D and E). The magnitude of bone loss in the gastric bypass group was similar by 24 months whether assessed by DXA or QCT, despite the fact that QCT did not detect any bone loss at the hip in the first 12 months after gastric bypass. Accordingly, from months 12 to 24, there was a marked decline in total vBMD at the hip, as assessed by QCT, in the gastric bypass group that was significantly greater than controls (−4.2 ± 1.0 vs 1.6 ± 1.1%; P = .001). By 24 months after gastric bypass surgery, trabecular vBMD of the hip was significantly lower than in controls (P < .001; Figure 2F), largely due to a higher rate of bone loss from months 12 to 24 in the gastric bypass group (−3.4 ± 1.1 vs 0.8 ± 0.8%; P = .018). At 24 months, the average DXA hip T-score in the gastric bypass group was 0.3 ± 1.1.

Changes in radius and tibia BMD, microarchitecture, and estimated strength

vBMD and key parameters of bone microarchitecture, assessed using HR-pQCT, deteriorated throughout the 24-month study in the gastric bypass group (see Supplemental Table 2). Total vBMD at the radius and tibia declined progressively after gastric bypass, such that vBMD was 9% lower than controls at month 24 for both the radius and the tibia (P < .001 for both; Figure 3, A and B). At the radius, this decrease was primarily due to a greater decline in trabecular vBMD in the gastric bypass group than controls (−8.6 ± 1.8 vs 1.1 ± 1.2%; P < .001) and was accompanied by a decrease in trabecular number and an increase in trabecular heterogeneity. At the tibia, the declines in cortical (−4.6 ± 1.2%) and trabecular vBMD (−4.1 ± 1.9%) after gastric bypass were similar and were significantly greater than controls (P ≤ .010 for both). Cortical porosity increased more in the gastric bypass group than in controls (65.4 ± 19.3 vs −4.5 ± 6.0%; P < .001). Cortical area decreased and trabecular area increased after gastric bypass at both the radius and the tibia. The patterns of reciprocal change in cortical and trabecular areas are consistent with the process of endocortical resorption. At month 24, the estimated failure load was 9–10% lower at the radius and the tibia after gastric bypass as compared with controls (Figure 4, A and B). Overall, the declines observed in bone density, microarchitecture, and estimated bone strength in the first 12 months were matched or exceeded by declines in the 12- to 24-month period after gastric bypass.

Figure 3. — Mean ± SEM percentage change in radius and tibia vBMD in gastric bypass (black bars) and control groups (white bars) over 24 months.

Total vBMD at the distal radius (A) and distal tibia (B) in the gastric bypass and control groups are shown at 12 and 24 months. *, P value < .05 for the comparison of gastric bypass vs control at each time point.

Figure 4. — Mean ± SEM percentage change in estimated failure load at the radius and tibia in gastric bypass (solid line) and control groups (dotted line) over 24 months.

Bone strength estimates of failure load at the distal radius (A) and distal tibia (B) in the gastric bypass and control groups over 24 months. *, P value < .05 for the comparison of gastric bypass vs control at each time point. RYGB, Roux-en-Y gastric bypass.

Change in calciotropic hormones and bone markers

Serum calcium and 25(OH)-vitamin D levels were stable throughout the 24-month study in both groups (Table 1). Although there were no differences in PTH between the gastric bypass and control groups over the first 12 months, by 24 months PTH was slightly higher in the gastric bypass group than in controls (54 ± 27 vs 49 ± 16 pg/mL; P = .017). Nevertheless, 76% of values in the gastric bypass group remained within the normal range of the PTH assay (15–65 pg/mL) at 24 months, which is similar to the proportion observed in the control group (82%; χ²P value = 0.72).

Serum CTX and PINP levels were unchanged in the control group but were markedly and persistently elevated in the gastric bypass group by 6 months, with mean CTX and PINP levels remaining 149 ± 20 and 65 ± 12% above baseline at 24 months (Table 1). The increase in CTX markedly exceeded that of PINP at all postoperative timepoints.

Predictors of bone loss within the gastric bypass group

Baseline age and weight were not predictors of 24-month changes in spine or hip BMD by DXA or QCT. Furthermore, neither 6-month nor 24-month changes in weight, serum calcium, 25(OH)-vitamin D, or PTH were significantly associated with 24-month changes in BMD. We also did not observe any suggestion of increased bone loss among the small subset of gastric bypass subjects who developed mild secondary hyperparathyroidism at 24 months. Lastly, increases in CTX at 6 months predicted bone loss at the spine as assessed by DXA (r = −0.47; P = .036) and QCT (r = −0.47; P = .040). There were also suggestions that 24-month increases in PINP and CTX were inversely associated with bone loss at the trabecular spine at 24 months (PINP, r = −0.47, P = .050; CTX, r = −0.46, P = .057).

Discussion

This study demonstrates that bone loss continues at both central and peripheral sites in the second year after Roux-en-Y gastric bypass despite weight stabilization by 6 months after surgery. At 24 months, bone density was 5–7% lower at the spine, 6–10% lower at the hip, and 9% lower at both the distal radius and tibia in subjects who had gastric bypass compared with nonsurgical obese controls. Declines in radius and tibia bone density were accompanied by trabecular deterioration at the radius, increased cortical porosity at the tibia, and increased endosteal bone resorption at both sites. These changes led to a 9–10% decrease in the estimated bone strength at these peripheral sites. Notably, serum calcium, 25(OH)-vitamin D, and PTH remained normal in most subjects over this 24-month period. Bone density in the nonsurgical control group was largely stable, likely due to a combination of their minimal weight change and relatively young age.

There has been uncertainty regarding the effect of gastric bypass surgery on bone density measures due to concerns about imaging artifacts in the setting of weight loss. Several aspects of our study provide strong evidence that bone loss after gastric bypass surgery is real. First, we obtained consistent results at multiple skeletal sites and using multiple imaging modalities. Second, although weight loss may cause bone density imaging artifacts in the initial months after gastric bypass (11), there is relative weight maintenance in the second year, and therefore the observed declines between years 1 and 2 can be interpreted without concern for artifact. Third, the increases in bone turnover markers are consistent with the observed bone loss, with early changes in CTX predicting 2-year vertebral bone loss. Lastly, we also documented concurrent negative changes in bone microarchitecture at peripheral sites. Of note, the observed deterioration in tibial cortical microarchitecture is in line with a shorter study of bone microarchitectural changes 1 year after bariatric surgery (8). In our 2-year study, estimated bone strength at the radius and tibia declined faster in the second year after gastric bypass than in the first.

The continued declines in bone density and estimated bone strength may have important clinical implications for long-term skeletal health in gastric bypass patients. The persistent elevation in bone turnover markers suggests that skeletal homeostasis has not yet been achieved by 2 years after gastric bypass surgery and is consistent with cross-sectional studies reporting that bone resorption markers are elevated in patients who underwent gastric bypass on average 3 years earlier (16, 17). One other study used DXA to investigate longitudinal changes in hip and spine bone density beyond 1 year and reported that spine and hip bone density declined an additional approximately 3% between years 1 and 3 after gastric bypass, although the absence of a control group hindered the ability to account for age-related changes (10). It should be noted that the preoperative bone density was high in most of the severely obese patients in this study, as is expected given the known effects of obesity on bone density. Therefore, despite the substantial amount of bone loss seen after 2 years, the average DXA T-scores for the gastric bypass cohort remained in the normal range. Because the relationship between bone density and fracture is altered in obese patients such that they fracture at higher bone density than normal-weight controls (18, 19), the changes observed after gastric bypass surgery may be clinically important. Additionally, accelerated bone loss over multiple years after gastric bypass might increase the risk for osteoporosis and skeletal fragility because rapid skeletal deterioration may have more pronounced effects on bone strength than predicted by bone mass measurements alone. We did not observe any fractures in the gastric bypass group during this 2-year study. Epidemiological data on fracture risk after bariatric surgery are limited, with short-term follow-up (∼2 y after surgery) showing no increase in fracture rates (20) but with longer-term follow-up (∼7 y after surgery) suggesting a 3-fold increase in spine fracture and a 5-fold increase in hip fracture (21). Because bone loss remains high in the second year after gastric bypass, monitoring of bone density after gastric bypass surgery appears to be warranted.

The mechanisms responsible for bone loss after gastric bypass are unknown. One commonly postulated theory is mechanical unloading of the skeleton due to substantial weight loss. Although some previous studies have found an association of weight loss and bone loss after gastric bypass (6, 22), we found that bone loss was not associated with weight loss. It is possible that this discrepancy may be due to study-related differences in DXA machines and/or acquisition techniques, which are variably impacted by obesity-related soft tissue artifacts (23, 24). In our study, bone loss persisted significantly beyond the 6-month point of weight stabilization. Moreover, the pattern of universally increased bone turnover after gastric bypass is unlike bed rest studies of mechanical unloading, which are characterized by an increase in bone resorption and a decrease in bone formation (25). Finally, rats that undergo gastric bypass have greater bone loss than sham-operated rats that are calorically restricted to achieve similar magnitudes of weight loss (26). These findings suggest that even if mechanical unloading plays a role in bone loss after gastric bypass, other factors are likely to be the principal drivers.

Malabsorption of calcium has also been implicated in the pathogenesis of bone loss after gastric bypass. One study has suggested a clinically insignificant decrease in intestinal calcium absorption (27), whereas another documented a marked decline (28). Although calcium malabsorption might cause decreases in bone density due to skeletal hypomineralization, this explanation appears less likely given that PTH levels were only minimally affected in these studies. In the current study, maintenance of serum calcium, vitamin D, and PTH levels largely in the normal range did not prevent significant bone loss after gastric bypass surgery, and changes in these parameters were not significant predictors of bone loss.

Altogether, these findings suggest that standard bone homeostatic mechanisms are not the principal pathways determining bone loss after gastric bypass. Gastric bypass surgery is accompanied by large changes in gastrointestinal, adipocytic, and neuroendocrine hormones, many of which are postulated to have direct or indirect effects on the skeleton (29, 30). Additional studies are needed to further determine the contribution of these complex physiological changes to bone loss after gastric bypass.

This study has several limitations. By 24 months, we experienced a dropout rate of 28%. However, characteristics of dropouts were similar to the overall cohort, including their 12-month bone density and laboratory changes, suggesting that the dropouts are unlikely to have biased the results. In addition, it remains to be seen whether the skeletal changes we observed are generalizable to other popular types of bariatric surgery or whether they are specific to gastric bypass. For example, previous studies suggest that adjustable gastric banding might be less harmful to bone, although skeletal changes after sleeve gastrectomy may be similar to those seen after gastric bypass (4, 31, 32).

In conclusion, we found progressive declines in bone density and bone microarchitecture and persistent increases in bone turnover markers in the second year after Roux-en-Y gastric bypass surgery. This skeletal deterioration occurs despite stabilization of weight and maintenance of normal calcium and vitamin D levels. Although the benefits of gastric bypass surgery on reducing obesity comorbidities are well established, the potential for adverse effects on skeletal integrity remains an important concern. Additional data are clearly needed to characterize the clinical impact of the observed bone loss and to assist in the development of rational approaches to address bone loss and fracture risk in patients who undergo bariatric surgery.

Supplementary Material

Supplemental_Table_1_and_2_REVISED

Supplemental_Table_1_and_2_REVISED.pdf^{(83.3KB, pdf)}

Acknowledgments

We thank Ms Robbin Cleary for bone density measurements, the Clinical Laboratory Research Core at the Massachusetts General Hospital for batch laboratory testing, and the nursing and dietary staff of the Mallinckrodt General Clinical Research Center for their dedicated care of the study participants.

This work was supported by National Institutes of Health (NIH) Grants K12 HD51959, K23 DK093713, and P30 DK046200. The Clinical Research Center was supported by NIH Grant 1 UL1 RR025758, and the HR-pQCT Core Facility was supported by NIH Grant S10 RR023405.

The content of the manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Clinical Trial Registration no. NCT01098942.

Disclosure Summary: The authors have nothing to disclose.

Abbreviations

aBMD: areal BMD
BMD: bone mineral density
CTX: type 1 cross-linked C-telopeptide
DXA: dual-energy x-ray absorptiometry
HR-pQCT: high-resolution peripheral QCT
PINP: procollagen type 1 N-terminal propeptide
QCT: quantitative computed tomography
vBMD: volumetric BMD.

References

1. Sturm R, Hattori A. Morbid obesity rates continue to rise rapidly in the United States. Int J Obes (Lond). 2013;37(6):889–891. [DOI] [PMC free article] [PubMed] [Google Scholar]
2. Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg. 2013;23(4):427–436. [DOI] [PubMed] [Google Scholar]
3. Chang SH, Stoll CR, Song J, Varela JE, Eagon CJ, Colditz GA. The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003–2012. JAMA Surg. 2014;149(3):275–287. [DOI] [PMC free article] [PubMed] [Google Scholar]
4. Yu EW. Bone metabolism after bariatric surgery. J Bone Miner Res. 2014;29(7):1507–1518. [DOI] [PMC free article] [PubMed] [Google Scholar]
5. Yu EW, Bouxsein ML, Roy AE, et al. Bone loss after bariatric surgery: discordant results between DXA and QCT bone density. J Bone Miner Res. 2014;29(3):542–550. [DOI] [PMC free article] [PubMed] [Google Scholar]
6. Fleischer J, Stein EM, Bessler M, et al. The decline in hip bone density after gastric bypass surgery is associated with extent of weight loss. J Clin Endocrinol Metab. 2008;93(10):3735–3740. [DOI] [PMC free article] [PubMed] [Google Scholar]
7. Coates PS, Fernstrom JD, Fernstrom MH, Schauer PR, Greenspan SL. Gastric bypass surgery for morbid obesity leads to an increase in bone turnover and a decrease in bone mass. J Clin Endocrinol Metab. 2004;89(3):1061–1065. [DOI] [PubMed] [Google Scholar]
8. Stein EM, Carrelli A, Young P, et al. Bariatric surgery results in cortical bone loss. J Clin Endocrinol Metab. 2013;98(2):541–549. [DOI] [PMC free article] [PubMed] [Google Scholar]
9. von Mach MA, Stoeckli R, Bilz S, Kraenzlin M, Langer I, Keller U. Changes in bone mineral content after surgical treatment of morbid obesity. Metabolism. 2004;53(7):918–921. [DOI] [PubMed] [Google Scholar]
10. Vilarrasa N, San José P, García I, et al. Evaluation of bone mineral density loss in morbidly obese women after gastric bypass: 3-year follow-up. Obes Surg. 2011;21(4):465–472. [DOI] [PubMed] [Google Scholar]
11. 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(1):119–124. [DOI] [PMC free article] [PubMed] [Google Scholar]
12. Putman MS, Yu EW, Lee H, et al. Differences in skeletal microarchitecture and strength in African-American and white women. J Bone Miner Res. 2013;28(10):2177–2185. [DOI] [PMC free article] [PubMed] [Google Scholar]
13. Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK. Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone. 2010;47(3):519–528. [DOI] [PMC free article] [PubMed] [Google Scholar]
14. Boutroy S, Van Rietbergen B, Sornay-Rendu E, Munoz F, Bouxsein ML, Delmas PD. Finite element analysis based on in vivo HR-pQCT images of the distal radius is associated with wrist fracture in postmenopausal women. J Bone Miner Res. 2008;23(3):392–399. [DOI] [PubMed] [Google Scholar]
15. Kriska AM, Knowler WC, LaPorte RE, et al. Development of questionnaire to examine relationship of physical activity and diabetes in Pima Indians. Diabetes Care. 1990;13(4):401–411. [DOI] [PubMed] [Google Scholar]
16. Goode LR, Brolin RE, Chowdhury HA, Shapses SA. Bone and gastric bypass surgery: effects of dietary calcium and vitamin D. Obes Res. 2004;12(1):40–47. [DOI] [PubMed] [Google Scholar]
17. Valderas JP, Velasco S, Solari S, et al. Increase of bone resorption and the parathyroid hormone in postmenopausal women in the long-term after Roux-en-Y gastric bypass. Obes Surg. 2009;19(8):1132–1138. [DOI] [PubMed] [Google Scholar]
18. Premaor MO, Pilbrow L, Tonkin C, Parker RA, Compston J. Obesity and fractures in postmenopausal women. J Bone Miner Res. 2010;25(2):292–297. [DOI] [PubMed] [Google Scholar]
19. Holbrook TL, Barrett-Connor E. The association of lifetime weight and weight control patterns with bone mineral density in an adult community. Bone Miner. 1993;20(2):141–149. [DOI] [PubMed] [Google Scholar]
20. Lalmohamed A, de Vries F, Bazelier MT, et al. Risk of fracture after bariatric surgery in the United Kingdom: population based, retrospective cohort study. BMJ. 2012;345:e5085. [DOI] [PMC free article] [PubMed] [Google Scholar]
21. Nakamura KM, Haglind EG, Clowes JA, et al. Fracture risk following bariatric surgery: a population-based study. Osteoporos Int. 2014;25(1):151–158. [DOI] [PMC free article] [PubMed] [Google Scholar]
22. Carrasco F, Ruz M, Rojas P, et al. Changes in bone mineral density, body composition and adiponectin levels in morbidly obese patients after bariatric surgery. Obes Surg. 2009;19(1):41–46. [DOI] [PubMed] [Google Scholar]
23. Tothill P, Laskey MA, Orphanidou CI, van Wijk M. Anomalies in dual energy x-ray absorptiometry measurements of total-body bone mineral during weight change using Lunar, Hologic and Norland instruments. Br J Radiol. 1999;72(859):661–669. [DOI] [PubMed] [Google Scholar]
24. Binkley N, Krueger D, Vallarta-Ast N. An overlying fat panniculus affects femur bone mass measurement. J Clin Densitom. 2003;6(3):199–204. [DOI] [PubMed] [Google Scholar]
25. Inoue M, Tanaka H, Moriwake T, Oka M, Sekiguchi C, Seino Y. Altered biochemical markers of bone turnover in humans during 120 days of bed rest. Bone. 2000;26(3):281–286. [DOI] [PubMed] [Google Scholar]
26. Abegg K, Gehring N, Wagner CA, et al. Roux-en-Y gastric bypass surgery reduces bone mineral density and induces metabolic acidosis in rats. Am J Physiol Regul Integr Comp Physiol. 2013;305(9):R999–R1009. [DOI] [PubMed] [Google Scholar]
27. Riedt CS, Brolin RE, Sherrell RM, Field MP, Shapses SA. True fractional calcium absorption is decreased after Roux-en-Y gastric bypass surgery. Obesity. 2006;14(11):1940–1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
28. Schafer AL, Weaver CM, Black DM, et al. Intestinal calcium absorption decreases dramatically after gastric bypass surgery, despite optimization of vitamin D status [published online January 31, 2015]. J Bone Miner Res. doi: 10.1002/jbmr.2467. [DOI] [PMC free article] [PubMed] [Google Scholar]
29. Folli F, Sabowitz BN, Schwesinger W, Fanti P, Guardado-Mendoza R, Muscogiuri G. Bariatric surgery and bone disease: from clinical perspective to molecular insights. Int J Obes (Lond). 2012;36(11):1373–1379. [DOI] [PubMed] [Google Scholar]
30. Brzozowska MM, Sainsbury A, Eisman JA, Baldock PA, Center JR. Bariatric surgery, bone loss, obesity and possible mechanisms. Obes Rev. 2013;14(1):52–67. [DOI] [PubMed] [Google Scholar]
31. Nogués X, Goday A, Peña MJ, et al. Bone mass loss after sleeve gastrectomy: a prospective comparative study with gastric bypass [in Spanish]. Cir Esp. 2010;88(2):103–109. [DOI] [PubMed] [Google Scholar]
32. Pluskiewicz W, Bužga M, Holéczy P, Bortlík L, Šmajstrla V, Adamczyk P. Bone mineral changes in spine and proximal femur in individual obese women after laparoscopic sleeve gastrectomy: a short-term study. Obes Surg. 2012;22(7):1068–1076. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplemental_Table_1_and_2_REVISED

Supplemental_Table_1_and_2_REVISED.pdf^{(83.3KB, pdf)}

[B1] 1. Sturm R, Hattori A. Morbid obesity rates continue to rise rapidly in the United States. Int J Obes (Lond). 2013;37(6):889–891. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B2] 2. Buchwald H, Oien DM. Metabolic/bariatric surgery worldwide 2011. Obes Surg. 2013;23(4):427–436. [DOI] [PubMed] [Google Scholar]

[B3] 3. Chang SH, Stoll CR, Song J, Varela JE, Eagon CJ, Colditz GA. The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003–2012. JAMA Surg. 2014;149(3):275–287. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B4] 4. Yu EW. Bone metabolism after bariatric surgery. J Bone Miner Res. 2014;29(7):1507–1518. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B5] 5. Yu EW, Bouxsein ML, Roy AE, et al. Bone loss after bariatric surgery: discordant results between DXA and QCT bone density. J Bone Miner Res. 2014;29(3):542–550. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B6] 6. Fleischer J, Stein EM, Bessler M, et al. The decline in hip bone density after gastric bypass surgery is associated with extent of weight loss. J Clin Endocrinol Metab. 2008;93(10):3735–3740. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B7] 7. Coates PS, Fernstrom JD, Fernstrom MH, Schauer PR, Greenspan SL. Gastric bypass surgery for morbid obesity leads to an increase in bone turnover and a decrease in bone mass. J Clin Endocrinol Metab. 2004;89(3):1061–1065. [DOI] [PubMed] [Google Scholar]

[B8] 8. Stein EM, Carrelli A, Young P, et al. Bariatric surgery results in cortical bone loss. J Clin Endocrinol Metab. 2013;98(2):541–549. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B9] 9. von Mach MA, Stoeckli R, Bilz S, Kraenzlin M, Langer I, Keller U. Changes in bone mineral content after surgical treatment of morbid obesity. Metabolism. 2004;53(7):918–921. [DOI] [PubMed] [Google Scholar]

[B10] 10. Vilarrasa N, San José P, García I, et al. Evaluation of bone mineral density loss in morbidly obese women after gastric bypass: 3-year follow-up. Obes Surg. 2011;21(4):465–472. [DOI] [PubMed] [Google Scholar]

[B11] 11. 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(1):119–124. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B12] 12. Putman MS, Yu EW, Lee H, et al. Differences in skeletal microarchitecture and strength in African-American and white women. J Bone Miner Res. 2013;28(10):2177–2185. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B13] 13. Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK. Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone. 2010;47(3):519–528. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B14] 14. Boutroy S, Van Rietbergen B, Sornay-Rendu E, Munoz F, Bouxsein ML, Delmas PD. Finite element analysis based on in vivo HR-pQCT images of the distal radius is associated with wrist fracture in postmenopausal women. J Bone Miner Res. 2008;23(3):392–399. [DOI] [PubMed] [Google Scholar]

[B15] 15. Kriska AM, Knowler WC, LaPorte RE, et al. Development of questionnaire to examine relationship of physical activity and diabetes in Pima Indians. Diabetes Care. 1990;13(4):401–411. [DOI] [PubMed] [Google Scholar]

[B16] 16. Goode LR, Brolin RE, Chowdhury HA, Shapses SA. Bone and gastric bypass surgery: effects of dietary calcium and vitamin D. Obes Res. 2004;12(1):40–47. [DOI] [PubMed] [Google Scholar]

[B17] 17. Valderas JP, Velasco S, Solari S, et al. Increase of bone resorption and the parathyroid hormone in postmenopausal women in the long-term after Roux-en-Y gastric bypass. Obes Surg. 2009;19(8):1132–1138. [DOI] [PubMed] [Google Scholar]

[B18] 18. Premaor MO, Pilbrow L, Tonkin C, Parker RA, Compston J. Obesity and fractures in postmenopausal women. J Bone Miner Res. 2010;25(2):292–297. [DOI] [PubMed] [Google Scholar]

[B19] 19. Holbrook TL, Barrett-Connor E. The association of lifetime weight and weight control patterns with bone mineral density in an adult community. Bone Miner. 1993;20(2):141–149. [DOI] [PubMed] [Google Scholar]

[B20] 20. Lalmohamed A, de Vries F, Bazelier MT, et al. Risk of fracture after bariatric surgery in the United Kingdom: population based, retrospective cohort study. BMJ. 2012;345:e5085. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B21] 21. Nakamura KM, Haglind EG, Clowes JA, et al. Fracture risk following bariatric surgery: a population-based study. Osteoporos Int. 2014;25(1):151–158. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B22] 22. Carrasco F, Ruz M, Rojas P, et al. Changes in bone mineral density, body composition and adiponectin levels in morbidly obese patients after bariatric surgery. Obes Surg. 2009;19(1):41–46. [DOI] [PubMed] [Google Scholar]

[B23] 23. Tothill P, Laskey MA, Orphanidou CI, van Wijk M. Anomalies in dual energy x-ray absorptiometry measurements of total-body bone mineral during weight change using Lunar, Hologic and Norland instruments. Br J Radiol. 1999;72(859):661–669. [DOI] [PubMed] [Google Scholar]

[B24] 24. Binkley N, Krueger D, Vallarta-Ast N. An overlying fat panniculus affects femur bone mass measurement. J Clin Densitom. 2003;6(3):199–204. [DOI] [PubMed] [Google Scholar]

[B25] 25. Inoue M, Tanaka H, Moriwake T, Oka M, Sekiguchi C, Seino Y. Altered biochemical markers of bone turnover in humans during 120 days of bed rest. Bone. 2000;26(3):281–286. [DOI] [PubMed] [Google Scholar]

[B26] 26. Abegg K, Gehring N, Wagner CA, et al. Roux-en-Y gastric bypass surgery reduces bone mineral density and induces metabolic acidosis in rats. Am J Physiol Regul Integr Comp Physiol. 2013;305(9):R999–R1009. [DOI] [PubMed] [Google Scholar]

[B27] 27. Riedt CS, Brolin RE, Sherrell RM, Field MP, Shapses SA. True fractional calcium absorption is decreased after Roux-en-Y gastric bypass surgery. Obesity. 2006;14(11):1940–1948. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B28] 28. Schafer AL, Weaver CM, Black DM, et al. Intestinal calcium absorption decreases dramatically after gastric bypass surgery, despite optimization of vitamin D status [published online January 31, 2015]. J Bone Miner Res. doi: 10.1002/jbmr.2467. [DOI] [PMC free article] [PubMed] [Google Scholar]

[B29] 29. Folli F, Sabowitz BN, Schwesinger W, Fanti P, Guardado-Mendoza R, Muscogiuri G. Bariatric surgery and bone disease: from clinical perspective to molecular insights. Int J Obes (Lond). 2012;36(11):1373–1379. [DOI] [PubMed] [Google Scholar]

[B30] 30. Brzozowska MM, Sainsbury A, Eisman JA, Baldock PA, Center JR. Bariatric surgery, bone loss, obesity and possible mechanisms. Obes Rev. 2013;14(1):52–67. [DOI] [PubMed] [Google Scholar]

[B31] 31. Nogués X, Goday A, Peña MJ, et al. Bone mass loss after sleeve gastrectomy: a prospective comparative study with gastric bypass [in Spanish]. Cir Esp. 2010;88(2):103–109. [DOI] [PubMed] [Google Scholar]

[B32] 32. Pluskiewicz W, Bužga M, Holéczy P, Bortlík L, Šmajstrla V, Adamczyk P. Bone mineral changes in spine and proximal femur in individual obese women after laparoscopic sleeve gastrectomy: a short-term study. Obes Surg. 2012;22(7):1068–1076. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Two-Year Changes in Bone Density After Roux-en-Y Gastric Bypass Surgery

Elaine W Yu

Mary L Bouxsein

Melissa S Putman

Elizabeth L Monis

Adam E Roy

Janey S A Pratt

W Scott Butsch

Joel S Finkelstein

Abstract

Context:

Objective:

Design and Setting:

Participants:

Outcomes:

Results:

Conclusions:

Subjects and Methods

Study subjects and protocol

DXA bone density

QCT bone density

HR-pQCT bone density and microarchitecture

Bionutrition measurements

Laboratory tests

Statistical analysis

Results

Baseline characteristics

Table 1.

Weight loss

Figure 1.

Changes in spine and total hip BMD

Figure 2.

Changes in radius and tibia BMD, microarchitecture, and estimated strength

Figure 3.

Figure 4.

Change in calciotropic hormones and bone markers

Predictors of bone loss within the gastric bypass group

Discussion

Supplementary Material

Acknowledgments

Abbreviations

References

Associated Data

Supplementary Materials

ACTIONS

PERMALINK

RESOURCES

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