Lipopolysaccharide-binding protein and bone health: data from a population-based sample of men.

We aimed to investigate the association between serum lipopolysaccharide-binding protein (LBP) and bone health in men. LBP was associated with lower bone density at the mid-forearm and the quantitative heel ultrasound measure, broadband ultrasound attenuation, for heavier participants. Data do not support clear associations between serum LBP and bone health. INTRODUCTION: The objective of this study was to investigate the association between serum lipopolysaccharide-binding protein (LBP) and potential downstream effects on skeletal density, quality, and turnover in a population-based sample of men. METHODS: This cross-sectional study utilised data from 1149 men (aged 20-96 year) enrolled in the Geelong Osteoporosis Study. Blood samples were obtained and lipopolysaccharide-binding protein (LBP), bone resorption marker, C-telopeptide (CTx), and formation marker, type 1 procollagen amino-terminal-propeptide (P1NP), were measured. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Stiffness Index (SI), broadband ultrasound attenuation (BUA), and speed of sound (SOS) were derived from quantitative heel ultrasound (QUS). Linear regression models were developed to test associations between log-transformed LBP (ln-LBP), BMD, QUS, and bone turnover, after adjusting for potential covariates. RESULTS: Serum LBP ranged from 1.07-208.53 ng/mL (median 16.53 ng/mL). Those with higher levels were older, less mobile, and had lower BMD at the mid-forearm, otherwise, groups were similar. Before and after adjustment for age, ln-LBP was associated with lower BMD at the spine, total body, and mid-forearm. Further adjustment for weight attenuated associations at the spine and total body, yet the relationship at the mid-forearm was sustained (ß - 0.014 ± 0.004, p = 0.001). SOS and SI were not associated with ln-LBP either before or after adjustment for age; however, weight was identified as an effect modifier in the relationship between ln-LBP and BUA. An association was observed for those weighing greater than 82.7 kg (ß 3.366 ± 0.929, p < 0.001), after adjustment for potential covariates. Neither bone turnover marker was associated with ln-LBP. CONCLUSION: Our data do not support a clear association between serum LBP and measures of bone health in this sample of men.

Bipolar disorder and bone health: A case-control study.

BACKGROUND: Bipolar disorder (BD) is associated with significant psychological and physical comorbidity. Yet little is known about the bone health of individuals with BD. Thus, we aimed to investigate the association between BD and bone health in a population-based sample of women. METHODS: Women with a history of BD (cases; n = 117) were recruited from public and private health care settings and controls, without BD, were drawn from the Geelong Osteoporosis Study (n = 909). BD was identified using a semi-structured clinical interview (SCID-I/NP). Bone mineral density (BMD) was measured at the spine, femoral neck and total body using dual energy x-ray absorptiometry, and bone quality by quantitative heel ultrasound and included the following parameters: Speed of Sound (SOS), Broadband Ultrasound Attenuation (BUA) and Stiffness Index (SI). Weight and height were measured and information on medication use and lifestyle was obtained. RESULTS: Adjusted mean BMD among the cases was 4.3% lower at the hip and 1.6% lower at the total body compared to controls. Age was an effect modifier at the spine. Among women <50 years, mean spine BMD for cases was 3.5% lower than controls. No differences in spine BMD for those ≥50 years were detected. Cases also had a 1.0%, 3.2% and 7.8% lower adjusted mean SOS, BUA and SI compared to controls, respectively. LIMITATIONS: Course, chronicity and recovery of BD were not explored in relation to bone health. CONCLUSION: These data suggest BD is associated with low bone quantity and quality in women. Replication and research into underlying mechanisms is warranted.

The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies.

The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.

Dietary tryptophan and bone health: a cross-sectional, population-based study.

Tryptophan metabolites influence bone. We aimed to investigate the relationship between dietary tryptophan and bone health in a population-based sample of men and women. Following adjustment for age, dietary tryptophan was not associated with bone quantity or quality, suggesting a non-critical role of superfluous tryptophan on the skeleton. PURPOSE: Tryptophan metabolites, such as serotonin, influence bone. We sought to determine the relationship between dietary intake of tryptophan and bone health in a population-based study of men and women. METHODS: Participants (1033 women and 900 men, aged 20-98 years) enrolled in the Geelong Osteoporosis Study (GOS) were investigated. Dietary information was collected using a validated questionnaire. Tryptophan levels were calculated (mg/day) in accordance with Food Standards Australia and New Zealand and dichotomised according to the median. Bone mineral density (BMD; g/cm2) was measured at the spine (postero-anterior projection) and total hip using dual-energy X-ray absorptiometry. Stiffness index (SI), broadband ultrasound attenuation (BUA) and speed of sound (SOS) were derived from quantitative heel ultrasound. Linear regression models were used to test associations between dietary tryptophan and bone health, after adjustment for potential confounders. RESULTS: Tryptophan intakes ranged from 112 to 3796 mg/day (median 1035) in men and 115-2869 mg/day (median 885) in women. In men older than 45 years and women, a high tryptophan intake was associated with greater hip BMD compared to participants with a low tryptophan intake (p = 0.002 and p = 0.04, respectively); however, these relationships were attenuated by age (all p > 0.05). Participants with high tryptophan intake had greater BUA and SI compared to participants with low tryptophan intake (men; BUA, p = 0.02 and SI, p = 0.02, and women; BUA, p = 0.03 and SI, p = 0.08), yet also attenuated by age (all p > 0.05). CONCLUSION: No association was found between tryptophan intake and bone health in this population, which suggests a non-critical role of superfluous tryptophan consumption on the skeleton.

Selective Serotonin Reuptake Inhibitors (SSRIs) and Markers of Bone Turnover in Men.

Selective serotonin reuptake inhibitors (SSRIs) have been shown to have a clinically significant impact on bone metabolism. To explore this further, we aimed to determine whether these agents are associated with serum markers of bone turnover utilising a population-based sample of men (n = 1138; 20-96 year) participating in the Geelong Osteoporosis Study. Blood samples were obtained and the bone resorption marker, C-telopeptide (CTx) and formation marker, type 1 procollagen amino-terminal-propeptide (PINP) were measured. Anthropometry and socio-economic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Lifetime mood disorders were assessed using semi-structured clinical interviews. Thirty-seven (3.3%) men reported using SSRIs. Age was an effect modifier in the association between SSRIs and markers of bone turnover. Among younger men (20-60 year; n = 557), adjusted mean CTx and PINP values were 12.4% [16.7 (95% CI 14.6-18.8) vs 19.1 (95% CI 18.7-19.4) pg/ml, p = 0.03] and 13.6% [5.6 (95% CI 4.9-6.3) vs 6.4 (95% CI 6.3-6.6) pg/ml, p = 0.02] lower among SSRI users compared to non-users, respectively. No differences in SSRI use and markers of bone turnover were detected among older men (61-94 year; all p > 0.05). These patterns persisted after further adjustment for activity, alcohol, smoking, SES, depression, bone active medications and other antidepressants. Our data suggest that SSRI use is associated with alterations in bone turnover markers among younger men. The observed decreases in both CTx and PINP are likely to contribute to a low bone turnover state and increased skeletal fragility with this potential imbalance between formation and resorption resulting in subsequent bone loss.