Skip to main content

Changes in bone mineral density after bariatric surgery in patients of different ages or patients with different postoperative periods: a systematic review and meta-analysis

Abstract

To assess changes in bone mineral density (BMD) following bariatric surgery (BS) in patients with different bone sites, postoperative periods and ages. Twenty-two studies were included. Femoral neck (FN) BMD decreased after surgery (MD, − 0.05 g/cm2, CI − 0.10 to − 0.01, P = 0.03). Postoperative BMD decreased more in the FN and lumbar spine (LS) of patients older than 40 (FNBMD, − 0.07 g/cm2, CI − 0.13 to − 0.00, P = 0.04; LSBMD, − 0.03 g/cm2, CI − 0.05 to − 0.00, P = 0.02) or patients with a postoperative time of greater than 12 months (FNBMD, − 0.06 g/cm2, CI − 0.12 to − 0.01, P = 0.03; LSMD, − 0.04 g/cm2, CI − 0.09 to 0.01, P = 0.12); therefore, post-BS bone loss should be monitored among patients in these groups. Longer follow-ups are needed to determine whether BMD changes or stabilizes.

Keypoints

What is already known?

  • Bariatric surgery (BS) in obese individuals has become increasingly popular.

  • BS can result in many complications, including osteoporosis. There are many reasons for this, including malabsorption and hormonal disorders.

  • It is necessary to investigate the association between BS and bone density.

What does this study add?

  • BS had a certain impact on many parts of the body, such as the femoral neck, lumbar spine and whole body.

  • The impact of metabolic surgery on bone density becomes more significant in participants aged 40 or older.

  • The impact of BS on bone density becomes greater in the patients with a postsurgical time of greater than 12 months.

How might your results change the direction of research or the focus of clinical practice?

BS had a certain impact on many parts of the body, particularly in patients over 40 years of age and individuals with a postsurgical time of greater than 12 months. These patients should pay attention to bone density screening and osteoporosis prevention. Further research is needed to analyze the variations over a longer period.

Introduction

Osteoporosis is a metabolic disease of the skeletal system characterized by reduced bone density and degeneration of the bone microstructure, leading to an increased risk of fracture and decreased quality of life [1]. It includes primary and secondary osteoporosis. The former includes type I (postmenopausal) osteoporosis, type II (senile) osteoporosis, and idiopathic osteoporosis. Secondary osteoporosis is caused by other diseases and/or drugs that affect bone metabolism. The diagnostic criteria of osteoporosis were established based on bone mineral density (BMD) by the World Health Organization (WHO) in 1994 [2]. BMD is reported as the T-score and Z score. The T-score describes the number of standard deviations (SDs) by which BMD differs from the mean value expected in young healthy individuals, while the Z score describes the number of SDs by which BMD differs from the mean value expected for age and sex. The WHO defines osteoporosis as a BMD of 2.5 or more SDs below that of a young adult (T-score) at any site. Among the different sampling sites, BMD measurement at the spine predicts spine fracture better than measures at other sites, while measurements of BMD taken at the hip predict hip fracture better than measurements taken at other sites [3]. BMD includes areal bone density (aBMD) and volumetric bone density (vBMD). Dual-energy X-ray absorptiometry (DXA) is the gold standard for measuring bone density [4]. Quantitative computed tomography (QCT) is used to quantify trabecular bone density [5], and QCT software allows both calculations of trabecular and cortical compartments. Therefore, QTC has recently been widely recognized as a method for diagnosing osteoporosis [6].

Osteoporosis occurs in both sexes and at different ages, but is most frequently seen in postmenopausal women and aging men. Approximately 200 million people worldwide are affected by osteoporosis [4]. Due to the current increase in the age of the world’s population, the impact of osteoporosis on the social economy and medicine is expected to become increasingly significant. In addition to osteoporosis, obesity is an important common global disease. The prevalence of morbid obesity has led to the wide application of bariatric surgery in recent years. There are seven procedures that either are currently or have been historically used: jejunoileal bypass (JIB), Roux-en-Y gastric bypass (RYGB), vertical-banded gastroplasty (VBG), biliopancreatic diversion (BPD), duodenal switch (DS), adjustable gastric banding (AGB), and sleeve gastrectomy (SG) [7]. Previous studies have shown that obesity might protect against osteoporosis [8,9,10], indicating that osteoporosis and obesity are closely related. However, a growing number of studies have revealed that metabolic surgery can affect bone quality and lead to bone loss, causing osteoporosis [11,12,13,14,15,16,17,18]. A meta-analysis published in 2016 showed that bone density at the femoral neck in patients with bariatric surgery decreased after the surgery compared to that in nonsurgical controls [15]. A recent meta-analysis indicated changes in bone metabolism after bariatric surgery, with a significant decrease in serum calcium and BMD but an increase in serum PTH [19]. There are several possible reasons for this, including malabsorption of calcium and vitamin D [20], decreased estrogen levels in women [21, 22], and several adipokine disorders [23].

None of the published meta-analyses included randomized clinical trials (RCTs) or discussed whether postoperative BMD changes over time. Nevertheless, some new results from RCTs have been published. Therefore, this meta-analysis was designed to investigate the changes in BMD after bariatric surgery in patients of different ages or patients with different postoperative periods.

Methods

Search strategy

We searched the PubMed, Embase, and Cochrane Library databases up to September 11, 2020, with no language restrictions. We searched for articles investigating the association of bariatric surgery with BMD or osteoporosis using the following keywords: "bariatric surgery", "Roux-en-Y gastric bypass", "vertical-banded gastroplasty", "biliopancreatic diversion", "duodenal switch", "adjustable gastric banding", "sleeve gastrectomy" AND "bone", "bone density", and "osteoporosis". This systematic review and meta-analysis was reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses [24].

Study selection

The inclusion criteria were as follows:

  1. (1)

    Study design: RCTs, observational studies;

  2. (2)

    Study subjects: all age groups from 18 to 80 years and both sexes;

  3. (3)

    Study intervention: bariatric surgery, without limitations of surgical approaches;

  4. (4)

    Study controls: no bariatric surgery (exercise, diet, medication, and no intervention); and

  5. (5)

    Outcomes: our primary outcome was the BMD of the different bone sites; the secondary outcome was the BMD of the different ages and postoperative periods.

The exclusion criteria were as follows:

  1. (1)

    Animal studies;

  2. (2)

    Reviews, case reports, editorials, comments, conference papers or abstracts, and letters; or

  3. (3)

    Studies that fit the topic but did not provide relevant data.

Data extraction

Two reviewers independently screened the articles, performed the quality assessment and extracted data according to the above criteria. The information from the included studies comprised: (1) general information including the name of the first author, publication year, and number of patients in each group; (2) study characteristics including the general data of the participants (age, sex) and interventions; and (3) outcomes including postoperative BMD (mean and standard deviation). Disagreements between the reviewers were resolved by discussion or by consulting a third reviewer. The Newcastle–Ottawa Quality Assessment Scale (NOS) was used to assess the quality of the literature. A score of 0–9 points was used to assess their quality. We considered a study to be high quality when the score was ≥ six points, and other studies were considered moderate quality. The Cochrane methodology was used to evaluate the quality of the included RCTs. Additionally, we evaluated the evidence level of the results using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework [25].

Statistical analysis

Statistical analysis was performed using RevMan 5.3 (freeware from the Cochrane Collaboration). Data were expressed as the mean difference (MD) or standardized mean difference (SMD) and 95% confidence intervals (CI). MDs were selected by comparing the same measurement method, and SMDs were used when comparing different measurement methods. The measurement method was DXA or QCT. If the article was divided into several subgroups according to age or sex, we merged them using the Excel calculation formula. We then conducted a homogeneity test on the included studies. The fixed-effects model was used when I2 < 50%, and the random-effects model was used when I2 ≥ 50%. Forest plots were used to visualize the results. Funnel plots were used for sensitivity analysis. Subgroup analyses were performed for different ages, time points after surgery, and surgical approaches. Originally, a subgroup analysis was performed based on baseline BMI categories to investigate the feasibility of bariatric surgery among individuals with a high BMI at baseline, but there was insufficient data regarding baseline BMI. P < 0.05 indicated significant differences. The protocol of this systematic review is registered in INPLACY (INPLACY 202130033).

Results

Included studies

Initially, 6417 articles were retrieved, and 1102 duplicate articles were deleted. All titles and abstracts (n = 5315) were analyzed according to research standards. A total of 179 articles were included in the preliminary screening. Further reading of the full text was performed, and finally, 22 [26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47] articles were included in the systematic review and meta-analysis. The flowchart is shown in Fig. 1.

Fig. 1
figure 1

Flowchart of literature screening

Characteristics of studies and subjects

The basic characteristics of the included literature are shown in Table 1. One article was in Spanish, and the rest were in English. A total of 3250 people were included (733 in the surgery group and 2517 in the control group). The quality of the 20 observational studies included was superior, and the scores on the Newcastle–Ottawa scale were ≥ 6 points. According to the NOS score, the studies were all high quality. Supplementary Fig. 1 shows the full risk of bias assessments for the two RCTs. The quality evaluation of the two RCTs is shown in Fig. 2. They were judged to be at unclear risk of bias for allocation concealment and blinding participants and personnel. The overall quality of evidence was rated using GRADE, as shown in Fig. 2. Ten studies included only male participants, one study included only female participants, and the remaining studies included both males and females. DXA and/or QCT were used to assess bone density. Twelve studies measured the BMD of the femoral neck, and 15 measured the BMD of the lumbar spine. Two articles were from the same database, and we chose one of them according to the location. For example, we chose one randomly if they both included the femoral neck data. If one of the articles contained other data we needed, we selected the data in that article.

Table 1 Basic characteristics of the included studies (n = 22)
Fig. 2
figure 2

GRADE

Association between bariatric surgery and BMD at different bone sites

Femoral neck BMD

Thirteen articles [26, 27, 32, 34, 35, 37, 38, 40,41,42, 44,45,46] analyzed the relationship between bariatric surgery and femoral neck BMD. As mentioned above, there were two articles from the same database. Thus, we identified 12 studies suitable for meta-analysis. There was heterogeneity among the 12 studies (I2 = 69%), so the random-effects model was used. The meta-analysis results showed that the bone density of the surgery group decreased more than that of the control group, and this difference was statistically significant (MD, − 0.05 g/cm2; 95% CI − 0.10 to − 0.01, P = 0.03) (Fig. 3a).

Fig. 3
figure 3

Forest plot of femoral neck BMD. a The forest plot of femoral neck BMD. b The forest plot of change from baseline of femoral neck BMD

Two studies [26, 44] did not match factors such as BMI at baseline, so the difference in bone density was used as an indicator. The two studies were homogeneous (I2 = 0%), so the fixed-effects model was used. The meta-analysis results showed that the bone density of the surgery group decreased more than that of the control group, and this difference was statistically significant (MD, − 0.09 g/cm2; 95% CI − 0.13 to − 0.04; P = 0.0004) (Fig. 3b).

Lumbar spine BMD

Fifteen [26, 28,29,30, 32, 34, 35, 37, 38, 40,41,42, 44, 45, 47] articles analyzed the relationship between bariatric surgery and lumbar spine BMD. The studies had significant heterogeneity (I2 = 93%), so the random-effects model was used. The bone density of the surgery group was lower than that of the control group (SMD, -0.28; 95% CI − 0.77 to 0.21; P = 0.26), but there was no significant difference between the results (P = 0.26) (Fig. 4a).

Fig. 4
figure 4

Forest plot of lumbar spine BMD. a Forest plot of lumbar spine BMD. b The forest plot of % change from baseline of lumbar spine BMD. c Forest plot of the change in lumbar spine BMD from baseline

Two [31, 33] RCTs assessed the percentage difference from baseline bone density in the lumbar spine. There was no significant heterogeneity among the 2 RCTs (I2 = 10%), so the fixed-effects model was used. The meta-analysis results showed that the bone density of the surgery group decreased more than that of the control group, but the difference was not significant (MD, − 1.92; 95% CI − 4.02 to 0.19; P = 0.07) (Fig. 4b).

Three studies [26, 28, 44] assessed the difference in bone density as an indicator. There was no significant heterogeneity among the study results (I2 = 43%); therefore, the fixed-effects model was used. The meta-analysis results showed that the bone density of the surgery group decreased more than that of the control group, and this difference was statistically significant (MD, − 0.04 g/cm2; 95% CI − 0.07 to − 0.01; P = 0.02) (Fig. 4c).

Total body BMD

Four [26, 34, 35, 39] articles analyzed the relationship between bariatric surgery and total body BMD. There was no heterogeneity between studies (I2 = 0%), so the fixed-effects model was used. The meta-analysis results showed that the bone density of the surgical group was 0.03 g/cm2 lower than that of the control group (MD, − 0.03 g/cm2; 95% CI − 0.04 to − 0.03; P < 0.00001) (Fig. 5).

Fig. 5
figure 5

Forest plot of total body BMD

The effect of different ages on BMD

Among the 12 articles assessing the association between femoral neck and bariatric surgery, there was one [27] article in which the average age of the subjects was less than 30 years; 5 [32, 35, 37, 41, 44] articles included 30- to 40-year-old patients; and 6 [34, 38, 40, 42, 45, 46] articles included patients older than 40 years of age. There was no significant heterogeneity among studies including 30- to 40-year-old patients (I2 = 12%), so the fixed-effects model was adopted. The bone density of the surgical group was 0.01 g/cm2 lower than that of the control group (MD, − 0.01 g/cm2; 95% CI − 0.06–0.04), but there was no significant difference between the results (P = 0.72). There was significant heterogeneity among studies including patients older than 40 years of age (I2 = 80%), so we used the random-effects model. There was a significant difference between the results of the surgery group and the control group (MD, − 0.07 g/cm2; 95% CI − 0.13 to − 0.00; P = 0.04) (Fig. 6a). A sensitivity analysis was performed to evaluate the robustness of these results. According to the results, the dataset from Heiskanen, J. T [38]. reported obvious deviation from the estimate. Heterogeneity was found to be significantly reduced following omission of the dataset of Heiskanen, J. T. (I2 = 51%; P = 0.07), revealing that heterogeneity may be increased by that study. According to the characteristics of the studies included in our meta-analysis, we considered that the major source of heterogeneity was age. The low heterogeneity in the subgroup analysis examining age supports this explanation.

Fig. 6
figure 6

The forest plot of BMD in different age ranges. a Forest plot of the femoral neck. b Forest plot of the lumbar spine

Among the 15 articles evaluating the relationship between bariatric surgery and the lumbar spine, there were 2 [26, 28] articles in which the average age of subjects was less than 30 years; 6 [32, 34, 35, 37, 41, 44] articles included 30- to 40-year-old patients; and 7 [29, 30, 34, 38, 40, 42, 45] articles included patients older than 40 years of age. The age division was not clear in one of the articles [47]; therefore, we did not include this in the subgroup analysis. One study [34] was divided into two groups based on age; for this reason, the sum of the above articles was higher than 1. There was no heterogeneity among the studies including patients younger than 30 years of age (I2 = 0%); therefore, we used the fixed-effects model. There was no significant difference between the results of the surgery group and the control group (SMD, − 0.03; 95% CI − 0.43 to − 0.37; P = 0.88). There was significant heterogeneity among studies including 30- to 40-year-old patients (I2 = 87%), so the random-effects model was adopted. The bone density of the surgical group was 0.04 g/cm2 lower than that of the control group (MD, − 0.04 g/cm2; 95% CI − 0.17 to 0.09), but there was no significant difference between the results (P = 0.55). There was no significant heterogeneity among studies of patients over 40 years of age (I2 = 42%); therefore, we used the fixed-effects model. There was a significant difference between the results of the surgery group and the control group (MD, − 0.03 g/cm2; 95% CI − 0.05 to − 0.00; P = 0.02) (Fig. 6b).

The time after surgery affects BMD

Among the 12 articles assessing the association between BMD of the femoral neck and bariatric surgery, there were 8 [27, 34, 35, 38, 40, 42, 45, 46] articles in which the postoperative time was more than 12 months, and 2 [41, 44] articles examined patients with a postoperative time of greater than 12 months. In the other 2 [32, 37] articles, the postoperative time was unclear. There was no heterogeneity among studies of patients with a postoperative time of less than 12 months (I2 = 0%), so the fixed-effects model was used. The results showed no significant difference between the results of the surgery group and the control groups (MD, − 0.06 g/cm2; 95% CI − 0.15 to 0.02, P = 0.15) (Fig. 7a). There was significant heterogeneity among studies of patients with a postoperative time of greater than 12 months (I2 = 75%); therefore, the random-effects model was used. The meta-analysis results showed that the bone density of the surgery group was lower than that of the control group, and this difference was statistically significant (MD, − 0.06 g/cm2; 95% CI − 0.12 to − 0.01; P = 0.03) (Fig. 7a).

Fig. 7
figure 7

Forest plot of BMD at different time points after surgery. a Forest plot of the femoral neck. b Forest plot of the lumbar spine

Among the 15 articles evaluating the relationship between bariatric surgery and lumbar spine, there were 9 [26, 30, 34, 35, 38, 40, 42, 45, 47] articles in which the postoperative time was greater than 12 months and 3 [28, 41, 44] articles in which the postoperative time was less than 12 months. The time in the rest of the articles was unclear. There was significant heterogeneity among the studies of patients with a postoperative time of less than 12 months (I2 = 85%), so a random-effects model was used. The results showed no significant difference between the surgery group and the control group (SMD, 0.12; 95% CI − 0.83 to 1.07; P = 0.80). There was also significant heterogeneity among the studies of patients with a postoperative time of greater than 12 months (I2 = 90%); therefore, the random-effects model was used. The meta-analysis results showed that the bone density of the surgery group was less than that of the control group, and the difference was not statistically significant (MD, − 0.04 g/cm2; 95% CI − 0.09 to 0.01; P = 0.12) (Fig. 7b). The results showed that removing any of the 9 studies had no significant effect, indicating that this meta-analysis was robust and reliable.

The different surgical procedures affect BMD

Of the 12 articles assessing the association between BMD of the femoral neck and bariatric surgery, the surgical approach was RYGB in 6 articles [32, 38, 40,41,42, 46], not RYGB in 3 articles [27, 44, 45], and unspecified in 3 articles. There was no significant heterogeneity among the studies examining RYGB (I2 = 25%), so the fixed-effects model was used. The results showed no significant difference between the surgery group and the control group (MD, -0.02 g/cm2; 95% CI − 0.05 to 0.02; P = 0.37) (Fig. 8a). There was significant heterogeneity among the studies that did not examine RYGB (I2 = 59%); therefore, the random-effects model was used. The meta-analysis results showed that the bone density of the surgery group was lower than that of the control group, and this difference was statistically significant (MD, − 0.12 g/cm2; 95% CI − 0.23 to − 0.01; P = 0.03) (Fig. 8a).

Fig. 8
figure 8

Forest plot of BMD with different surgical approaches. a Forest plot of the femoral neck. b Forest plot of the lumbar spine

Among the 15 articles evaluating the relationship between bariatric surgery and the lumbar spine, the surgical approach was RYGB in 5 articles [32, 38, 40,41,42], not RYGB in 6 articles [26, 28, 30, 44, 47], and unspecified in the remaining articles. There was no significant heterogeneity among the studies examining RYGB (I2 = 47%), so the fixed-effects model was used. The results showed a significant difference between the surgery and control groups (SMD, 0.27; 95% CI 0.03–0.50; P = 0.03). There was significant heterogeneity among the studies that did not examine RYGB (I2 = 93%); therefore, the random-effects model was used. The meta-analysis results showed that the bone density of the surgery group was lower than that of the control group, and this difference was statistically significant (MD, − 0.08 g/cm2; 95% CI − 0.16 to − 0.01; P = 0.03) (Fig. 8b).

Publication bias

The funnel plots were created from BMD at two locations, including the femoral neck and lumbar spine, to assess for the presence of publication bias. Supplementary Fig. 2-a shows that the funnel plot (the femoral neck from 12 studies) may have a small sample effect, but it was symmetrical, indicating that the possibility of research publication bias was small. The funnel plot of the lumbar spine was relatively symmetrical and did not indicate publication bias (Supplementary Fig. 2).

Discussion

The findings of our meta-analyses were as follows: compared with the control groups, BMD of the femoral neck obviously declined in the bariatric surgery groups. However, there was no difference in the BMD decrease of the lumbar spine in the intervention groups; subjects older than 40 years had a lower BMD than those patients younger than 40 years at the femoral neck and lumbar spine following bariatric surgery; and bone density decreased more significantly one year after metabolic surgery.

In the present study, a much greater reduction in femoral neck density was found in the intervention groups. This finding was consistent with those of previous studies [15, 18]. The decrease in BMD of the femoral neck was significant following bariatric surgery [48]. The potential mechanism could be as follows. First, bariatric surgery caused reduced alimentary intake or absorption through restriction of the stomach or digestive tract. Additionally, bariatric surgery resulted in secondary hyperparathyroidism, malabsorption of nutrients, reduced mechanical load, and changes in fat and intestinal hormones [49]. As a result, bariatric surgery could lead to calcium/vitamin D malabsorption. Studies have shown that weight loss achieved through dietary restrictions, drugs, or bariatric surgery could lead to a decrease in BMD. However, the loss of bone mass following metabolic surgery is more severe [50].

However, no difference in bone density at the lumbar spine was observed between the intervention groups and the controls. Additionally, in the comparison of the changes in BMD before and after bariatric surgery, a marked decrease was observed, indicating that bariatric surgery resulted in a decline in the BMD of the lumbar spine. The following reasons may explain this discrepancy. First, the measurement of BMD using DXA may be confounded by several factors [18, 51]. A tiny change in marrow composition can have a marked effect on the X-ray absorptivity due to the volumetric preponderance of marrow over that of the trabecular bone volume [52]. Second, an increased content of adipose tissue in the bone marrow could weaken bone strength [53]. Zhu’s study demonstrated that marrow adipose tissue (MAT) of the lumbar spine increased, while MAT of the peripheral skeleton decreased one year after sleeve gastrectomy [54]. Although the related literature is limited, the conclusion could still provide recommendations for further research. Given that a lower BMD was associated with a higher risk of fracture [55], close monitoring of bone density postoperatively seemed to be necessary to detect the risk of fracture earlier.

Next, our results showed a significant decrease in participants aged 40 or older, but no difference in those younger than 40 years after bariatric surgery. Therefore, the impact of metabolic surgery on bone density might be greater in patients older than 40 years. Several factors may be responsible for this difference. First, loss of bone density was linked to a relative deficiency in sex hormone effects, including decreases in testosterone and estradiol levels with aging [56]. Previous studies reported that males with hypogonadism had a much lower BMD [57, 58]. However, a prospective study on 31 patients (23 RYGB and 8 controls) showed that there was a significant elevation in testosterone 6 months after surgery [59]. Coincidentally, a prospective randomized controlled long-term trial [60] compared surgical and nonsurgical weight loss impacts on sex hormones among morbidly obese men (10 patients and 10 controls). The total testosterone and free testosterone levels increased visibly in the intervention group 2 years after gastric bypass surgery [60]. Another prospective study on 32 patients who underwent RYGB demonstrated that these patients had a significant increase in total testosterone and sex hormone-binding globulin during the fourth postoperative year [61]. However, they did not stratify the subjects according to age, which might have influenced the results in their study. Ovarian function began to decrease at 40 years of age, and androgen levels decreased rapidly at age 40. Hence, patients with metabolic surgery after the age of 40 might have a smaller increase in testosterone or other sex hormones than before the age of 40. However, there are no relevant reports in the literature. Furthermore, weight recovery was critical because BMI was also an important predictor of low BMD. Napoli’s study suggested that increased cortical porosity led to alterations in bone structure [62]. Specifically, they [62] demonstrated that adolescents with obesity had greater cortical porosity at peripheral sites than normal-weight controls, as weight loss following bariatric surgery might reduce or reverse this effect [51]. Third, leptin also seemed to be an important mediator influencing the relationship between fat mass and BMD. The synthesis of leptin increases with age [63], and circulating leptin levels are negatively correlated with BMD [64]. Therefore, attention should be devoted to patients who are older than 40 years. This finding may be beneficial for evidence-based decision-making by clinicians.

In addition, to better clarify whether BMD changed over time, we analyzed alterations in the BMDs of the patients at greater than 12 months postoperatively. The BMD in the surgery group was significantly lower than that in the control group in the current study. Recent studies [65] have shown that bariatric surgery is associated with bone loss in adolescents [65]. These studies demonstrated a decrease in BMD across 2 years following surgery, from abnormally high preoperative levels toward the average reference range, but longer follow-ups were needed to determine whether bone mass would continue to change or stabilize. Therefore, long-term follow-up is needed to determine whether the decrease in BMD would continue and increase the risk for future fractures.

Furthermore, we divided the surgical methods into RYGB and non-RYGB (NRYGB). Our results showed that the bone density of the NRYGB group decreased significantly compared with that of the RYGB group. Interestingly, the bone density of the lumbar spine significantly increased in the RYGB group. This result was inconsistent with previous studies [66, 67] reporting that RYGB may lead to bone loss. In this meta-analysis, five articles belonged to the RYGB group. Among these articles, only one showed that BMD was lower than that in controls [38]. The possible explanations for the differences are as follows. First, the values of BMD at baseline were different in the four studies. Therefore, incomplete matching might also affect the results of this study. Second, as mentioned above, alterations in the distribution of adipose tissue led to changes in bone measurements. Thus, further investigations are needed to confirm this conclusion.

Limitations

There are some limitations in the current meta-analysis. First, most of the selected studies were observational studies, and only two RCTs were included. Second, the number of studies focused on adolescents was few. Finally, various subgroup analyses were done to explore the factors influencing heterogeneity, including different body sites, ages, duration after surgery and surgical approaches. Due to the limitation of the length of this paper, and the changes of bone metabolism after bariatric surgery had been stated in previous meta-analysis [18]. So, analyses of indicators of bone metabolism (e.g., vitamin and trace element supplementation) were not performed in this study.

Conclusion

In summary, our findings showed a decrease in BMD at different body sites. It should be noted that BMD declined more after surgery in the femoral neck and lumbar spine in adults over 40 years old and at postoperative periods greater than 12 months. Bone density screening and fracture prevention strategies should be emphasized for those patients. Additionally, a longer follow-up is still needed to determine whether bone mass changes or stabilizes.

Availability of data and materials

Not applicable.

References

  1. Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006. https://doi.org/10.1007/s00198-006-0172-4.

    Article  PubMed  Google Scholar 

  2. Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int. 1994;4(6):368–81.

    Article  CAS  PubMed  Google Scholar 

  3. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285(6):785–95.

    Article  Google Scholar 

  4. Di Paola M, Gatti D, Viapiana O, et al. Radiofrequency echographic multispectrometry compared with dual X-ray absorptiometry for osteoporosis diagnosis on lumbar spine and femoral neck. Osteoporos Int. 2019;30(2):391–402.

    Article  PubMed  Google Scholar 

  5. Xu XM, Li N, Li K, et al. Discordance in diagnosis of osteoporosis by quantitative computed tomography and dual-energy X-ray absorptiometry in Chinese elderly men. J Orthop Translat. 2019;18:59–64.

    Article  PubMed  Google Scholar 

  6. Engelke K, Adams JE, Armbrecht G, et al. Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD Official Positions. J Clin Densitom. 2008;11(1):123–62.

    Article  PubMed  Google Scholar 

  7. Buchwald H. The evolution of metabolic/bariatric surgery. Obes Surg. 2014;24(8):1126–35.

    Article  PubMed  Google Scholar 

  8. Zhao LJ, Liu YJ, Liu PY, et al. Relationship of obesity with osteoporosis. J Clin Endocrinol Metab. 2007;92(5):1640–6.

    Article  CAS  PubMed  Google Scholar 

  9. Reid IR, Ames R, Evans MC, et al. Determinants of total body and regional bone mineral density in normal postmenopausal women–a key role for fat mass. J Clin Endocrinol Metab. 1992;75(1):45–51.

    CAS  PubMed  Google Scholar 

  10. Ravn P, Cizza G, Bjarnason NH, et al. Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group. J Bone Miner Res. 1999;14(9):1622–7.

    Article  CAS  PubMed  Google Scholar 

  11. Ablett AD, Boyle BR, Avenell A. Fractures in adults after weight loss from bariatric surgery and weight management programs for obesity: systematic review and meta-analysis. Obes Surg. 2019;29(4):1327–42.

    Article  PubMed  Google Scholar 

  12. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724–37.

    Article  CAS  PubMed  Google Scholar 

  13. Chaves Pereira De Holanda N, De Lima Carlos I, Chaves De Holanda Limeira C, et al. Fracture Risk After Bariatric Surgery: A Systematic Literature Review and Meta-Analysis. Endocr Pract, 2021.

  14. Huang TW, Chen JY, Wu YL, et al. Alterations of bone markers in obese patients with type 2 diabetes after bariatric surgery: a meta-analysis and systemic review of randomized controlled trials and cohorts. Medicine. 2021;100(20): e26061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ko BJ, Myung SK, Cho KH, et al. Relationship between bariatric surgery and bone mineral density: a meta-analysis. Obes Surg. 2016;26(7):1414–21.

    Article  PubMed  Google Scholar 

  16. Rodríguez-Carmona Y, López-Alavez FJ, González-Garay AG, et al. Bone mineral density after bariatric surgery. A systematic review. Int J Surg. 2014;12(9):976–82.

    Article  PubMed  Google Scholar 

  17. Zhang Q, Chen Y, Li J, et al. A meta-analysis of the effects of bariatric surgery on fracture risk. Obes Rev. 2018;19(5):728–36.

    Article  CAS  PubMed  Google Scholar 

  18. Liu C, Wu D, Zhang JF, et al. Changes in bone metabolism in morbidly obese patients after bariatric surgery: a meta-analysis. Obes Surg. 2016;26(1):91–7.

    Article  PubMed  Google Scholar 

  19. World Health Organization. Obesity and overweight. 2021. Accessed 9 June 2021.

  20. Cashman KD. Calcium intake, calcium bioavailability and bone health. Br J Nutr. 2002;87(Suppl 2):S169–77.

    Article  CAS  PubMed  Google Scholar 

  21. Wang Y, Hernandez G, Mack WJ, et al. Retrospective analysis of phytoSERM for management of menopause-associated vasomotor symptoms and cognitive decline: a pilot study on pharmacogenomic effects of mitochondrial haplogroup and APOE genotype on therapeutic efficacy. Menopause. 2020;27(1):57–65.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Pouillès JM, Trémollières F, Bonneu M, et al. Influence of early age at menopause on vertebral bone mass. J Bone Miner Res. 1994;9(3):311–5.

    Article  PubMed  Google Scholar 

  23. Gimble JM, Zvonic S, Floyd ZE, et al. Playing with bone and fat. J Cell Biochem. 2006;98(2):251–66.

    Article  CAS  PubMed  Google Scholar 

  24. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7): e1000097.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis—a 2020 practice parameter update, systematic review, and grading of recommendations, assessment, development and evaluation (GRADE) analysis. J Allergy Clin Immunol. 2020;145(4):1082–123.

    Article  CAS  PubMed  Google Scholar 

  26. Misra M, Singhal V, Carmine B, et al. Bone outcomes following sleeve gastrectomy in adolescents and young adults with obesity versus non-surgical controls. Bone. 2020;134: 115290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Misra M, Animashaun A, Bose A, et al. Impact of sleeve gastrectomy on hip structural analysis in adolescents and young adults with obesity. Surg Obes Relat Dis. 2020. https://doi.org/10.1016/j.soard.2020.07.020.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bredella MA, Singhal V, Hazhir Karzar N, et al. Effects of sleeve gastrectomy on bone marrow adipose tissue in adolescents and young adults with obesity. J Clin Endocrinol Metab. 2020. https://doi.org/10.1210/clinem/dgaa581.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Tangalakis LL, Tabone L, Spagnoli A, et al. Effects of Roux-en-Y gastric bypass on osteoclast activity and bone density in morbidly obese patients with type 2 diabetes. Obes Surg. 2019;30(1):290–5.

    Article  Google Scholar 

  30. Iki M, Fujita Y, Kouda K, et al. Increased risk of osteoporotic fracture in community-dwelling elderly men 20 or more years after gastrectomy: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study. Bone. 2019;127:250–9.

    Article  PubMed  Google Scholar 

  31. Crawford MR, Bena JF, Schauer PR, et al. Long term outcomes of bariatric surgery on bone density in obese patients with type 2 diabetes. J Diabetes Complications. 2017;31(4):780–1.

    Article  PubMed  Google Scholar 

  32. Menegati GC, De Oliveira LC, Santos AL, et al. Nutritional status, body composition, and bone health in women after bariatric surgery at a University Hospital in Rio de Janeiro. Obes Surg. 2016;26(7):1517–24.

    Article  PubMed  Google Scholar 

  33. Maghrabi AH, Wolski K, Abood B, et al. Two-year outcomes on bone density and fracture incidence in patients with T2DM randomized to bariatric surgery versus intensive medical therapy. Obesity. 2015;23(12):2344–8.

    Article  PubMed  Google Scholar 

  34. Hintze LJ, Cremon AS, Bevilaqua CA, et al. Factors associated with bone mineral density in women who underwent bariatric surgery. Acta Sci Health Sci. 2014;36(1):105–12.

    Article  Google Scholar 

  35. Costa TL, Paganotto M, Radominski RB, et al. Calcium metabolism, vitamin D and bone mineral density after bariatric surgery. Osteoporos Int. 2014;26(2):757–64.

    Article  PubMed  CAS  Google Scholar 

  36. 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. 2013;29(3):542–50.

    Article  CAS  Google Scholar 

  37. De Vasconcelos RS, Viégas M, Marques TF, et al. Factors associated with secondary hyperparathyroidism in premenopausal women undergoing Roux-en-y gastric bypass for the treatment of obesity. Arq Bras Endocrinol Metabol. 2010;54(2):233–8.

    Article  PubMed  Google Scholar 

  38. 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):1132–8.

    Article  PubMed  Google Scholar 

  39. Gómez JM, Vilarrasa N, Masdevall C, et al. Regulation of bone mineral density in morbidly obese women: a cross-sectional study in two cohorts before and after bypass surgery. Obes Surg. 2009;19(3):345–50.

    Article  PubMed  Google Scholar 

  40. De La Maza MP, Leiva L, Barrera G, et al. Nutritional status, body composition and bone mineral density in gastric bypass females: impact of socioeconomic level][J. Rev Med Chil. 2008;136(11):1415–23.

    PubMed  Google Scholar 

  41. Pereira FA, De Castro JA, Dos Santos JE, et al. Impact of marked weight loss induced by bariatric surgery on bone mineral density and remodeling. Braz J Med Biol Res. 2007;40(4):509–17.

    Article  CAS  PubMed  Google Scholar 

  42. Goode LR, Brolin RE, Chowdhury HA, et al. Bone and gastric bypass surgery: effects of dietary calcium and vitamin D. Obes Res. 2004;12(1):40–7.

    Article  CAS  PubMed  Google Scholar 

  43. Coates PS, Fernstrom JD, Fernstrom MH, et al. 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):1061–5.

    Article  CAS  PubMed  Google Scholar 

  44. Guney E, Kisakol G, Ozgen G, et al. Effect of weight loss on bone metabolism: comparison of vertical banded gastroplasty and medical intervention. Obes Surg. 2003;13(3):383–8.

    Article  PubMed  Google Scholar 

  45. Heiskanen JT, Kröger H, Pääkkönen M, et al. Bone mineral metabolism after total gastrectomy. Bone. 2001;28(1):123–7.

    Article  CAS  PubMed  Google Scholar 

  46. Ott MT, Fanti P, Malluche HH, et al. Biochemical evidence of metabolic bone disease in women following Roux-Y gastric bypass for morbid obesity. Obes Surg. 1992;2(4):341–8.

    Article  CAS  PubMed  Google Scholar 

  47. Inoue K, Shiomi K, Higashide S, et al. Metabolic bone disease following gastrectomy: assessment by dual energy X-ray absorptiometry. Br J Surg. 1992;79(4):321–4.

    Article  CAS  PubMed  Google Scholar 

  48. Zhao LJ, Jiang H, Papasian CJ, et al. Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. J Bone Miner Res. 2008;23(1):17–29.

    Article  CAS  PubMed  Google Scholar 

  49. Lupoli R, Lembo E, Saldalamacchia G, et al. Bariatric surgery and long-term nutritional issues. World J Diabetes. 2017;8(11):464–74.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Shapses SA, Riedt CS. Bone, body weight, and weight reduction: what are the concerns? J Nutr. 2006;136(6):1453–6.

    Article  CAS  PubMed  Google Scholar 

  51. Misra M, Bredella MA. Bone metabolism in adolescents undergoing bariatric surgery. J Clin Endocrinol Metab. 2021;106(2):326–36.

    Article  PubMed  Google Scholar 

  52. Bolotin HH. DXA in vivo BMD methodology: an erroneous and misleading research and clinical gauge of bone mineral status, bone fragility, and bone remodelling. Bone. 2007;41(1):138–54.

    Article  CAS  PubMed  Google Scholar 

  53. Misra M, Katzman DK, Cord J, et al. Bone metabolism in adolescent boys with anorexia nervosa. J Clin Endocrinol Metab. 2008;93(8):3029–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhu M, Hao G, Xing J, et al. Bone marrow adipose amount influences vertebral bone strength. Exp Ther Med. 2019;17(1):689–94.

    PubMed  Google Scholar 

  55. Kanis JA, Mccloskey EV, Harvey NC, et al. Intervention thresholds and the diagnosis of osteoporosis. J Bone Miner Res. 2015;30(10):1747–53.

    Article  PubMed  Google Scholar 

  56. Jeffcoat M. The association between osteoporosis and oral bone loss. J Periodontol. 2005;76(11 Suppl):2125–32.

    Article  PubMed  Google Scholar 

  57. Devogelaer JP, De Cooman S, De Deuxchaisnes CN. Low bone mass in hypogonadal males. Effect of testosterone substitution therapy, a densitometric study. Maturitas. 1992;15(1):17–23.

    Article  CAS  PubMed  Google Scholar 

  58. Behre HM, Kliesch S, Leifke E, et al. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab. 1997;82(8):2386–90.

    Article  CAS  PubMed  Google Scholar 

  59. Samavat J, Cantini G, Lotti F, et al. Massive weight loss obtained by bariatric surgery affects semen quality in morbid male obesity: a preliminary prospective double-armed study. Obes Surg. 2018;28(1):69–76.

    Article  PubMed  Google Scholar 

  60. Reis LO, Favaro WJ, Barreiro GC, et al. Erectile dysfunction and hormonal imbalance in morbidly obese male is reversed after gastric bypass surgery: a prospective randomized controlled trial. Int J Androl. 2010;33(5):736–44.

    Article  CAS  PubMed  Google Scholar 

  61. International Diabetes Federation. IDF Diabetes Atlas (10th ed). https://www.idf.org/e-library/epidemiology-research/diabetes.html. 2021.

  62. Napoli N, Chandran M, Pierroz DD, et al. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. 2017;13(4):208–19.

    Article  CAS  PubMed  Google Scholar 

  63. Li H, Matheny M, Nicolson M, et al. Leptin gene expression increases with age independent of increasing adiposity in rats. Diabetes. 1997;46(12):2035–9.

    Article  CAS  PubMed  Google Scholar 

  64. Kontogianni MD, Dafni UG, Routsias JG, et al. Blood leptin and adiponectin as possible mediators of the relation between fat mass and BMD in perimenopausal women. J Bone Miner Res. 2004;19(4):546–51.

    Article  CAS  PubMed  Google Scholar 

  65. Kaulfers AM, Bean JA, Inge TH, et al. Bone loss in adolescents after bariatric surgery. Pediatrics. 2011;127(4):e956–61.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Alexandrou A, Armeni E, Kouskouni E, et al. Cross-sectional long-term micronutrient deficiencies after sleeve gastrectomy versus Roux-en-Y gastric bypass: a pilot study. Surg Obes Relat Dis. 2014;10(2):262–8.

    Article  PubMed  Google Scholar 

  67. Vix M, Liu KH, Diana M, et al. Impact of Roux-en-Y gastric bypass versus sleeve gastrectomy on vitamin D metabolism: short-term results from a prospective randomized clinical trial. Surg Endosc. 2014;28(3):821–6.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Funded by National Key Research and Development Program of China (2018YFC2001100-5), Natural Science Foundation of China (No. 82070878).

Funding

National Key Research and Development Program of China (2018YFC2001100-5), Natural Science Foundation of China (No. 82070878).

Author information

Authors and Affiliations

Authors

Contributions

XDO, MGC, and LZX contributed equally to the study. XDO, MGC, and LZX performed the research; contributed to the conception and design of the study, the acquisition of data, and the analysis and interpretation of data; drafted all versions of the article; and approved the final version for publication. WL, HH, and GC contributed to the conception and design of the study, all revisions, and the final approval for publication. JW contributed to the conception and design of the study, the analysis and interpretation of data, all revisions, and the final approval for publication. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Huibin Huang or Junping Wen.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Figure S1.

Cochrane risk of bias. Figure S2. The forest plot.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ou, X., Chen, M., Xu, L. et al. Changes in bone mineral density after bariatric surgery in patients of different ages or patients with different postoperative periods: a systematic review and meta-analysis. Eur J Med Res 27, 144 (2022). https://doi.org/10.1186/s40001-022-00774-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s40001-022-00774-0

Keywords

  • Bariatric surgery
  • Bone mineral density
  • Osteoporosis