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. Author manuscript; available in PMC: 2015 Aug 1.
Published in final edited form as: Arthritis Care Res (Hoboken). 2014 Aug;66(8):1233–1240. doi: 10.1002/acr.22270

Association between Inflammatory Biomarkers and Bone Mineral Density in a Community-based Cohort of Men and Women: The Framingham Osteoporosis Study

Todd R Sponholtz 1, Xiaochun Zhang 2, Joao DT Fontes 3,4, James B Meigs 5,6, L Adrienne Cupples 7, Douglas P Kiel 2,6,8, Marian T Hannan 2,6,8, Robert R McLean 2,6,8
PMCID: PMC4069198  NIHMSID: NIHMS549426  PMID: 24375982

Abstract

OBJECTIVE

Based upon evidence in animal and in-vitro studies, we tested the hypothesis that higher serum concentrations of the cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and the inflammatory marker C-reactive protein (CRP) would be inversely associated with BMD in a community-based cohort of men and women, with the strongest associations among post-menopausal women not using menopausal hormone therapy (MHT).

METHODS

We ascertained fasting serum concentrations of IL-6, TNF-α, and CRP and measured BMD at the femoral neck, trochanter, total femur, and spine (L2-L4) using dual energy X-ray absorptiometry in 2,915 members of the Framingham Offspring cohort (1996 to 2001). We used multivariable linear regression to estimate the difference (β) in BMD at each bone site associated with a one-unit increase in log-transformed serum concentrations of IL-6, TNF-α, and CRP separately for men (n=1,293), pre-menopausal women (n=231), post-menopausal women using MHT (n=498), and post-menopausal women not using MHT (n=893).

RESULTS

Inflammatory biomarkers were not associated with BMD in men. Among premenopausal women, there were statistically significant, modest inverse associations between IL-6 and trochanter BMD (β=−0.030, p<0.01), and between CRP and femoral neck (β=−0.015, p=0.05) and trochanter BMD (β=−0.014, p=0.04). TNF-α, was positively associated with spine BMD (β=0.043, p=0.01). In post-menopausal MHT users, CRP was positively associated with femoral neck BMD (β=0.011, p=0.04). There were no associations among post-menopausal women not using MHT.

CONCLUSIONS

The lack of consistency in our results suggests that elevated circulating concentration of inflammatory biomarkers may not be a risk factor for low BMD.

Introduction

Osteoporosis, characterized by the progressive loss of bone mass leading to increased fracture risk, is among the most common rheumatic diseases. The lifetime risk for an osteoporotic fracture in the US is estimated at 39.7% for women and 13.1% for men (1). Osteoporosis-related fracture is associated with considerable morbidity (2) and mortality (3) in older adults. Given the anticipated increase in the proportion of older adults in the population over the next several decades, it is critical to identify modifiable risk factors to aid in the prevention and treatment of osteoporosis.

Animal and in vitro studies support the hypothesis that pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) influence the age- and estrogen-related decrease in bone mineral density (BMD). These immune factors have been shown to promote the proliferation, activity, and survival of osteoclasts while inhibiting survival of osteoblasts (4-7). IL-6 (8) and C-reactive protein (CRP) (9), an acute-phase protein used as a general marker of inflammation, are present at low levels in the blood of young adults, but rise with increasing age as BMD concurrently declines. Furthermore, estrogen status is an important determinant of inflammation among women. The decline of estrogen at menopause is associated with rapid increases in serum inflammatory markers and decreases in BMD (4, 6), while menopausal hormone therapy (MHT), promotes maintenance of BMD (10-11) and decreases levels of several inflammatory biomarkers (12). Thus, cytokines could be important mediators of the decline in BMD associated both with aging and estrogen deficiency.

In spite of this, epidemiologic studies of pro-inflammatory cytokines and BMD have produced mixed results. Associations with BMD have been reported for soluble IL-6 receptor (8) and CRP (13), however many other studies have not observed cross-sectional associations between serum concentrations of IL-6, TNF-α, or CRP and BMD (8, 14-17). Most of the studies conducted to this point have included only women (8, 13-15, 17-20), with particular focus on postmenopausal women (17-20). Thus, relatively little is known about associations between inflammatory markers and BMD in men or premenopausal women. We therefore investigated the associations of circulating concentrations of IL-6, TNF-α, and CRP with BMD of the hip and spine among middle-aged and older men and women of the community-based Framingham Offspring study. We hypothesized that serum concentrations of these biomarkers would be inversely associated with BMD. Because estrogen status may influence cytokine production, we further posited that the association would be strongest among those with the lowest estrogen status, particularly post-menopausal women not using menopausal hormone therapy.

Methods

Study population

The Framingham Offspring Study began in 1971 with the main objective of investigating the role of familial risk factors for coronary artery disease among the children of the Framingham Study Original Cohort and their spouses (21). The 5,124 Offspring participants who enrolled at baseline have returned at approximately 4-year intervals for extensive physical examinations, comprehensive questionnaires, anthropometric measurements, blood chemistries, and assessment of cardiovascular and other risk factors by trained clinical personnel. The current study is comprised of the 2,915 Offspring men and women who had BMD measures of the hip and spine obtained as part of the Framingham Osteoporosis Study from 1996 to 2001, and at least one of the following serum inflammatory biomarkers measured from 1998 to 2001: IL-6, TNF-α, high-sensitivity CRP (CRP). This study was approved by the institutional review boards at Hebrew SeniorLife and Boston University and informed consent was obtained from all participants.

Inflammatory Biomarkers

Fasting morning serum samples were collected and stored at or below −70°C. Serum concentrations of total (free+bound) IL-6 (pg/mL) and high-sensitivity total TNF-α (pg/mL) were measured by using commercially available enzyme-linked immunoassay kits (R&D Systems, Minneapolis, Minnesota). The averages of duplicate samples were used in the analysis. Serum CRP (mg/L) was measured once using a high-sensitivity assay (BN100 nephelometer, Dade Behring, Deerfield, Illinois). The intra-assay coefficients of variation (CV) for IL-6, TNF-α and CRP were 3.1%, 6.6%, and 3.2%, respectively. TNF-α concentrations were available only among a subset of 76% of participants.

Bone mineral density

BMD of the proximal right femur (femoral neck, trochanter, total femur) and the lumbar spine (average BMD of L2–L4) was measured in grams per square centimeter (g/cm2) by a Lunar DPX-L (Lunar Radiation Corporation, Madison, WI, U.S.A.). Using standard positioning as recommended by the manufacturer, the right femur was scanned unless there was a history of previous fracture or hip joint replacement, in which case the left side was scanned. The CVs for the DPX-L were 1.7%, 2.5% and 0.9% for the femoral neck, trochanter and lumbar spine, respectively (22).

Other variables

Information on covariates was ascertained from measures collected at the time of BMD assessment and included sex, age (years), height (inches), body mass index (BMI, kg/m2), physical activity level, current smoking status (yes/no), and, in women, current use of menopausal hormone therapy (yes/no) and menopause status (post-menopausal: yes/no). Height without shoes was measured to the nearest quarter inch with a stadiometer. Weight was measured to the nearest pound using a standard balance beam scale with participants in light clothing and no shoes. BMI was calculated as weight in kg divided by the square of height in meters. Physical activity level was assessed using the Physical Activity Scale for the Elderly (PASE), a validated questionnaire of self-reported activity over the past seven days (23). Participants were classified as a current smoker if they reported regularly smoking cigarettes in the year prior to BMD measurement. Women were considered current menopausal hormone therapy users if they reported use (oral, patch or cream) at the time of the BMD assessment. Post-menopausal status at the time of BMD measurement was defined as having no menstrual periods for more than one year or current use of menopausal hormone therapy.

Statistical analysis

Distributions of IL-6, TNF-α, and CRP were right skewed and therefore logarithmically transformed prior to analyses. Because associations of IL-6, TNF-α, and CRP with BMD may be non-linear, inflammatory biomarkers were also categorized into quartiles. CRP was also categorized according to established clinical cut-points: low (<1 mg/L), borderline (1-3 mg/L), moderately high (3.01-10 mg/L), and markedly high concentrations (>10 mg/L) (24-26).

Analyses were first conducted within the whole cohort, and then separately within the following four groups of participants based on sex, menopause status and menopausal hormone therapy use: 1) men, 2) pre-menopausal women, 3) post-menopausal women using menopausal hormone therapy, and 4) post-menopausal women not using menopausal hormone therapy. For continuous biomarkers, multivariable linear regression was used to calculate the difference in BMD at each bone site (femoral neck, trochanter, total femur, lumbar spine) associated with a one unit increase in the log-transformed inflammatory biomarker. For quartiles and clinical CRP categories, least squares-adjusted mean BMD was compared among categories and a test for linear trend was calculated. Results of continuous, quartile and CRP clinical cut-point analyses indicated similar associations, thus only results using the continuous, log-transformed biomarkers are presented. Models were adjusted for covariates known to be important determinants of both BMD and biomarker concentration: sex (for whole cohort analyses only), age, height, BMI, physical activity and current smoking status. All statistical analyses were conducted using SAS/STAT software version 9.2 (SAS Institute Inc., Cary, NC).

Results

Characteristics of the 2,915 men and women at the time of BMD assessment are described in Table 1. The mean age of the study population was 61 and ranged from 29 to 86. Among the 1,622 women, 1,391 (86%) were post-menopausal, and 36% of post-menopausal women were current users of menopausal hormone therapy. Post-menopausal women using menopausal hormone therapy were younger and more physically active than those not using menopausal hormone therapy. Median serum concentrations of IL-6 and TNF-α were greater in men compared to pre-menopausal women and post-menopausal women using menopausal hormone therapy, but similar to post-menopausal women not using menopausal hormone therapy. CRP was highest in post-menopausal women using menopausal hormone therapy, likely due to the known increase in serum CRP concentrations with oral menopausal hormone therapy use (27-28). As expected, BMD at all sites was highest among men and decreased successively for pre-menopausal women, post-menopausal women using menopausal hormone therapy, and post-menopausal women not using menopausal hormone therapy.

Table 1.

Descriptive characteristics of men and women in the Framingham Offspring Study with inflammatory biomarkers (1998-2001) and hip or spine BMD (1996-2001).

Post-menopausal women
Characteristic* Men Premenopausal women Using menopausal hormone therapy Not using menopausal hormone therapy
N 1293 231 498 893
Age (years) 61± 9 48 ± 4 59 ± 7 64 ± 8
Height (in) 68.9 ± 2.7 64.7 ± 2.4 63.7 ± 2.3 63.0 ± 2.4
BMI (kg/m2) 28.8 ± 4.5 27.2 ± 6.5 26.9 ± 5.3 27.9 ± 5.6
Physical activity (PASE) 157 ± 87 162 ± 77 138 ± 72 125 ± 67
% current cigarette smoker 12 13 13 13
IL-6 (pg/mL)
    Median (inter-quartile range) 2.85 (1.85, 4.57) 2.09 (1.43, 3.04) 2.44 (1.71, 3.80) 2.91 (1.95, 4.54)
TNF-α (pg/mL)
    Median (inter-quartile range) 1.23 (0.97, 1.62) 1.03 (0.77, 1.69) 1.14 (0.83, 1.53) 1.29 (0.98, 1.67)
CRP (mg/L)
    Median (inter-quartile range) 1.92 (0.95, 4.36) 1.4 (0.59, 3.95) 3.89 (1.50, 7.77) 2.34 (1.06, 5.08)
Bone mineral density (g/cm2)
    Femoral neck 0.973 ± 0.138 0.969 ± 0.133 0.894 ± 0.129 0.829 ± 0.137
    Trochanter 0.884 ± 0.140 0.785 ± 0.127 0.738 ± 0.126 0.683 ± 0.134
    Total femur 1.042 ± 0.145 1.007 ± 0.133 0.938 ± 0.135 0.874 ± 0.147
    Lumbar spine 1.317 ± 0.204 1.264 ± 0.156 1.202 ± 0.193 1.098 ± 0.195
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*

Mean ± SD, unless otherwise indicated

In the whole study population, there were no statistically significant associations between log-transformed serum concentrations of IL-6, TNF-α and CRP and BMD at any site (data not shown). Among men, serum biomarkers were not associated with BMD at either the hip or spine as all regression coefficients were not significantly different from zero (Table 2). Among premenopausal women (Table 3), each unit increase in log-transformed serum IL-6 was associated with 0.030 g/cm2 lower trochanter BMD (p<0.01). Similar associations were observed for the femoral neck (β=-0.023, p=0.07) and total femur (β=−0.19, p=0.12), yet they were not statistically significant. CRP was also negatively associated with trochanter BMD in premenopausal women (β-0.014, P=0.04), and there were borderline statistically significant associations with BMD at the femoral neck (β=−0.015, P=0.05) and total femur (β=−0.011, p=0.14). Neither IL-6 nor CRP was associated with lumbar spine BMD in pre-menopausal women. TNF-α, however, was positively associated with lumbar spine BMD (β=0.043, p=0.01) among pre-menopausal women, though not with hip BMD.

Table 2.

Multivariable-adjusteda linear regression coefficients (β) for the association of log-transformed IL-6, TNF-α and CRP with BMD of the hip and spine among men of the Framingham Offspring cohort.

Neck Trochanter Total Femur Lumbar spine
β b P-value β P-value β P-value β P-value
IL-6 (pg/mL) 0.003 0.57 −0.002 0.67 0.001 0.86 0.009 0.28
TNF-α (pg/mL) −0.004 0.64 −0.012 0.22 −0.009 0.35 −0.014 0.33
CRP (mg/L) −0.006 0.11 −0.005 0.20 −0.005 0.22 −0.007 0.24
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a

Models adjusted for age, BMI, height, physical activity (PASE) and smoking

b

Difference in BMD for each 1 unit increase in log-transformed IL-6, TNF-α or CRP

Table 3.

Multivariable-adjusteda linear regression coefficients (β) for the association of log-transformed IL-6, TNF-α and CRP with BMD of the hip and spine among pre-menopausal women of the Framingham Offspring cohort.

Neck Trochanter Total Femur Lumbar spine
β b P-value β P-value β P-value β P-value
IL-6 (pg/mL) −0.023 0.07 −0.030 <0.01 −0.019 0.12 −0.001 0.94
TNF-α (pg/mL) 0.014 0.31 0.007 0.55 0.012 0.36 0.043 0.01
CRP (mg/L) −0.015 0.05 −0.014 0.04 −0.011 0.14 0.001 0.90
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a

Models adjusted for age, BMI, height, physical activity (PASE) and smoking

b

Difference in BMD for each 1 unit increase in log-transformed IL-6, TNF-α or CRP

IL-6 and TNF-α were not associated with BMD at either the hip or the spine for post-menopausal women, regardless of menopausal hormone therapy use (Table 4). Among post-menopausal women not using menopausal hormone therapy, there was no association between CRP and BMD at any site. CRP was, however, positively associated with femoral neck BMD among those using menopausal hormone therapy (β=0.011, p=0.04). Positive associations were also seen for CRP at the trochanter and total femur, although they were not statistically significant.

Table 4.

Multivariable-adjusteda linear regression coefficients (β) for the association of log-transformed IL-6, TNF-α and CRP with BMD of the hip and spine among post-menopausal women of the Framingham Offspring cohort.

Neck Trochanter Total Femur Lumbar spine
β b P-value β P-value β P-value β P-value
Using menopausal hormone therapy
    IL-6 (pg/mL) 0.011 0.20 0.009 0.25 0.010 0.24 0.010 0.43
    TNF-α (pg/mL) −0.005 0.69 −0.004 0.74 −0.008 0.50 −0.025 0.20
    CRP (mg/L) 0.011 0.04 0.007 0.16 0.009 0.10 0.008 0.35
Not using menopausal hormone therapy
    IL-6 (pg/mL) −0.007 0.22 −0.009 0.10 −0.007 0.27 −0.005 0.55
    TNF-α (pg/mL) −0.008 0.38 0.001 0.89 −0.005 0.61 −0.006 0.64
    CRP (mg/L) 0.004 0.28 0.002 0.56 0.004 0.28 0.006 0.30
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a

Models adjusted for age, BMI, height, physical activity (PASE) and smoking

b

Difference in BMD for each 1 unit increase in log-transformed IL-6, TNF-α or CRP

Discussion

In this study of middle-aged and older men and women of the Framingham Offspring cohort, we found inverse relations of serum concentrations of IL-6 and CRP with hip BMD only in pre-menopausal, though the magnitudes of these associations were small. A one standard deviation decrease in BMD is associated with roughly double the risk of fracture, depending upon the BMD site and the type of fracture (29-31). The differences in BMD we observed in association with serum concentrations of inflammatory biomarkers represent small fractions of a standard deviation, and thus would be expected to have a negligible impact on fracture risk. Furthermore, we detected a positive association between TNF-α and lumbar spine BMD in premenopausal women, and between CRP and femoral neck BMD in post-menopausal women using menopausal hormone therapy. Therefore, our findings indicate that elevated circulating concentration of inflammatory biomarkers may not be an important risk factor for low BMD.

Associations between inflammatory biomarkers and BMD in prior epidemiologic studies have been inconsistent. Papadapoulos et al. found positive correlations between serum IL-6 levels and BMD at five of six bone sites measured in the study (18). Zheng et al. reported correlations between secretion of IL-1β, IL-6, and TNF-α by stimulated peripheral monocyte blood cells and lumbar spine BMD (32). Recently, de Pablo et al. found that BMD of the total body, as well as sub-regions, decreased with increasing quintiles of serum CRP concentration (33). However, as in our study, several other analyses of markers of inflammation and BMD have failed to find any associations (8, 14-17). There are several possible reasons for these inconsistencies. First, signaling from cytokines such as IL-6 can have both inflammatory and anti-inflammatory effects (34-35). The effects of IL-6, TNF-α, and CRP on bone remodeling in vivo may therefore depend on the influence of other factors, such as other cytokines, receptors, and hormones not measured in these studies (7, 36). For example, both IL-6 (37) and TNF-α (38) signaling is influenced by the presence of soluble receptors. The soluble receptors for TNF-α have a longer half-life in serum than TNF-α itself (39), and their presence may relate to inflammation severity (38). Furthermore, soluble IL-6 receptor increases the half-life of IL-6, and studies in mice indicate that it may be required for the effect of IL-6 on osteoclastogenesis (40). Thus, the circulating concentrations of soluble receptors may be more relevant to bone than IL-6 and TNF-α themselves. Unfortunately, these measures were not available in our study.

Additionally, it may be that the local action of cytokines in the bone microenvironment, which is not easily measured in large epidemiologic studies, are more important for BMD than circulating, systemic concentrations. Nevertheless, serum and plasma measures of the cytokines examined in the current study have been linked to outcomes in several disease states, including rheumatoid arthritis (41-42), cardiovascular disease (43), and dementia (44), as well as in aging (45). Finally, sufficient variability in a single BMD measurement could obscure any effect of chronic, low level inflammation on bone mass, particularly if such an effect were to act slowly over a long period of time. Thus, chronic inflammation may be more relevant to the rate of bone loss than the absolute BMD value at a single time point. This is supported by two previous longitudinal studies. Ding et al. found direct relationships between IL-6, CRP, and TNF-α levels and three-year decreases in BMD, and also showed that IL-6 was the primary biomarker predictor of BMD in models containing all three cytokines (46). Furthermore, Scheidt-Nave et al. found that IL-6 predicted three-year decreases in total hip BMD in the first 10 years of menopause, but not thereafter (19). Additional longitudinal studies are required to help elucidate the relation between circulating concentrations of inflammatory cytokines and loss of BMD.

In the present study, there were statistically significant, though modest, inverse associations of IL-6 and CRP concentrations with BMD at the femoral neck and trochanter in pre-menopausal women only. This finding runs counter to our hypothesis that this association would be strongest in post-menopausal women not undergoing hormone replacement, who would be expected to have the lowest estrogen status. The reason for this discrepancy is unclear. However, Scheidt-Nave found that bone loss was greatest at the beginning of menopause, and that the association between IL-6 and bone loss was only apparent in the first decade after menopause. In addition, Slemenda et al. found that late peri-menopausal women (distinguished by irregular menses and elevated follicle stimulating hormone levels) had decreased estrogen concentrations compared to early peri-menopausal women, and were beginning to lose bone mass at the mid-radius (47). If our pre-menopausal group included a substantial number of perimenopausal women, these effects during the menopausal transition could explain our findings in this subgroup. Unfortunately our limited information on classifying menopausal status precludes exploration of this possibility. Along the same lines, since our definition of post-menopausal women not taking estrogen did not account for time since menopause, the mixing of early and late post-menopausal women could have obscured an association between IL-6 and BMD in this group. We have no explanation for the observed positive association between TNF-α concentration and lumbar spine BMD in pre-menopausal women. However, we are, to the best of our knowledge, the first to examine associations between circulating inflammatory cytokine levels in a large group of pre-menopausal women, and our observations require confirmation in other studies.

Also contrary to our hypothesis, we observed a modest yet positive association between CRP concentration and femoral neck BMD in post-menopausal women using menopausal hormone therapy. There were similar, though not significant, associations between CRP and the other hip sites. CRP is an acute-phase protein produced in the liver and regulated, in part, by IL-6, and TNF-α (48). Although often used as a marker for systemic inflammation, low-level increases in CRP may be seen with non-inflammatory conditions (49) and with exogenous estrogen treatments (27-28). In contrast, menopausal hormone therapy has been reported to decrease TNF-α levels, though its relation with IL-6 is not clear (12). Indeed, in our study post-menopausal women taking menopausal hormone therapy had the highest median concentration of CRP. Since menopausal hormone therapy is associated with reduced bone loss, our finding of a positive association between CRP and BMD in this group is not surprising. Our study is, to our knowledge, among the first to examine the relation of circulating inflammatory biomarkers with BMD among men. While men have generally higher BMD than women, the incidence of osteoporosis in men is not trivial (50). Thus, it is important to find factors that may be useful for identifying men at the highest risk for low BMD. Although women have a higher overall inflammatory burden, this gap narrows with aging as men tend to have an accelerated rate of increase in inflammation (51). While inflammatory biomarkers are a potential tool for distinguishing men at high risk for low BMD, we did not find evidence to support this. If such a relation exists, it may be more easily identified longitudinally than in a cross-sectional study such as ours.

Among the limitations of this study is its cross-sectional design, which precludes the ability to establish causal relationships between serum inflammatory biomarker levels and BMD. We also measured serum biomarkers at a single point in time. Such measurements may not accurately reflect the long-term level of inflammation in an individual. Nevertheless, studies of the variability of repeated CRP measurements over time have concluded that they are relatively stable and comparable to measures of total cholesterol (52-54). Repeated measurements of TNF-α and IL-6 are likewise reported to be stable (52, 55), although one group concluded a single measurement of IL-6 was not a sufficiently accurate measure of an individual's inflammatory status (55). Our observations about the effect of estrogen were based on groups that would be expected to differ by estrogen status, rather than on specific biomarkers of sex hormones. We cannot exclude the possibility that unmeasured confounding impacted our results. A major strength of this study is the use of data from the Framingham Offspring Cohort. This well-characterized cohort allowed us the opportunity to observe associations between inflammatory biomarkers and BMD in substantial numbers of middle-aged and older adults expected to differ by estrogen status. We also had information on numerous potential confounders of the association of interest. Yet because the Framingham Offspring cohort is primarily Caucasian, the generalizability of our results to other racial and ethnic groups is limited.

In conclusion, our results suggest that circulating concentrations of the inflammatory biomarkers IL-6, TNF-α and CRP may not be useful for identifying individuals at risk for low BMD. Despite our findings, there remains strong biological evidence that inflammation contributes to poor bone health, and circulating biomarkers have been associated with increased fracture risk in cohort studies (56-57). Further large, epidemiologic studies, preferably longitudinal and with direct measurement of estrogen, are needed to establish a definitive relation between inflammatory biomarkers and bone health, and whether bone loss is the causal link between inflammation and fracture. Other bone parameters that determine bone strength, such as bone structure and microarchitecture, that are not captured by two-dimensional BMD measures should also be explored. Additionally, more work is needed to develop tools that can assess inflammation at the bone microenvironment level and that are practical for implementation in large clinical studies. Confirmation of the hypothesized relation between inflammation and bone health could have important implications for the both the prediction and treatment of low bone mass, as such findings would potentially support the use of inflammatory biomarkers as tools to identify those at risk for low BMD, and espouse the development of anti-inflammatory interventions as a means to maintain bone health.

Significance and Innovation.

  • Increased activity of pro-inflammatory cytokines may be a risk factor for low bone mineral density (BMD) in the general community, yet epidemiologic evidence is inconsistent.

  • While prior studies of the relation between circulating inflammatory biomarkers and bone mineral density (BMD) focused primarily on post-menopausal women, we examined different subgroups of estrogen status defined by menopause and use of menopausal hormone therapy (MHT), as well as men.

  • Serum concentrations of inflammatory biomarkers were inversely related to hip BMD in premenopausal women, and directly related to spine BMD in premenopausal women and hip BMD in post-menopausal women using MHT, though associations were weak, and no relations were observed for men or postmenopausal women using MHT.

  • Findings from this cross-sectional study indicate that serum inflammatory biomarkers may not be useful for identifying those at risk for low BMD, though this should be confirmed with longitudinal studies of bone loss.

Acknowledgments

Support: Financial support provided by the American College of Rheumatology Research and Education Foundation Health Professional New Investigator Award, the Beth Israel Deaconess Medical Center/Harvard National Institutes of Health T32 Translational Research in Aging Training Program; the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging (R01 AR/AG041398, R01 AG028321), the National Heart, Lung and Blood Institute (R01 HL064753, R01 HL076784), the National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK080140) and the National Heart, Lung and Blood Institute's Framingham Heart Study (N01HC25195). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosures: Dr. Kiel has received grants from Eli Lilly, Merck Sharpe and Dohme and serves on the consulting boards for Eli Lilly, Merck Sharpe and Dohme, Amgen, Novartis.

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