Selective serotonin reuptake inhibitors (SSRIs) may reduce bone mineral density (BMD). Here, we investigate whether variants of the serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene moderate this association in boys.
Between November 2005 and August 2009, medically healthy boys, aged 7 to 17 years, were enrolled in a cross-sectional study exploring the effect of risperidone-induced hyperprolactinemia on BMD. Volumetric BMD of the ultradistal radius was measured using peripheral quantitative computed tomography, and areal BMD of the lumbar spine was estimated using dual energy x-ray absorptiometry. Multiple linear regression analysis tested whether the 5-HTTLPR genotypes interacted with SSRI treatment status to affect BMD, adjusting for relevant confounders. Participant enrollment was conducted at the University of Iowa, Iowa City.
Of 108 boys (mean ± SD age = 11.7 ± 2.8 years), with DSM-IV clinical diagnoses based on chart review, 52% (n = 56) had been taking an SSRI for a median duration of 2.8 years. After adjusting for pubertal development, anthropometric measures, physical activity, calcium intake, and prolactin concentration, there was a significant 5-HTTLPR genotype × SSRI treatment interaction effect on total lumbar spine BMD z score (P < .05) in non-Hispanic whites. The interaction effect on BMD at the ultradistal radius failed to reach statistical significance. Among LS genotype carriers, those treated with SSRIs had lower lumbar BMD z score and trabecular BMD at the radius compared to those not treated (P < .02 and P < .008, respectively).
These findings add to the growing evidence implicating the serotonin system in bone metabolism. They suggest the potential use of 5-HTTLPR genotypes to guide the safer long-term prescribing of SSRIs in youths. However, prospective confirmation in a controlled matched population is warranted.
Recent studies have demonstrated an important role for circulating serotonin in regulating bone mass in rodents. In addition, patients treated with selective serotonin reuptake inhibitors (SSRIs) have reduced areal bone mineral density (aBMD). However, the potential physiologic role of serotonin in regulating bone mass in humans remains unclear. Thus we measured serum serotonin levels in a population-based sample of 275 women and related these to total-body and spine aBMD assessed by dual-energy X-ray absorptiometry, femur neck total and trabecular volumetric BMD (vBMD) and vertebral trabecular vBMD assessed by quantitative computed tomography (QCT), and bone microstructural parameters at the distal radius assessed by high-resolution peripheral QCT (HRpQCT). Serotonin levels were inversely associated with body and spine aBMD (age-adjusted R = −0.17 and −0.16, P < .01, respectively) and with femur neck total and trabecular vBMD (age-adjusted R = −0.17 and −0.25, P < .01 and < .001, respectively) but not lumbar spine vBMD. Bone volume/tissue volume, trabecular number, and trabecular thickness at the radius were inversely associated with serotonin levels (age-adjusted R = −0.16, −0.16, and −0.14, P < .05, respectively). Serotonin levels also were inversely associated with body mass index (BMI; age-adjusted R = −0.23, P < .001). Multivariable models showed that serotonin levels remained significant negative predictors of femur neck total and trabecular vBMD, as well as trabecular thickness at the radius, after adjusting for age and BMI. Collectively, our data provide support for a physiologic role for circulating serotonin in regulating bone mass in humans. © 2010 American Society for Bone and Mineral Research
serotonin; bone density; bone structure; SSRI; osteoporosis
Adiponectin and leptin are hormones secreted by adipose cells that may impact bone mineral density (BMD). Few studies have evaluated the longitudinal association of leptin and adiponectin levels with rates of BMD change.
Hip and whole body areal BMD (aBMD) were measured 5 times using dual energy x-ray absorptiometry (DXA) over 10 years. Trabecular lumbar spine volumetric BMD (vBMD) was measured using quantitative computed topography (QCT) at baseline and year 6 in the Pittsburgh cohort only. Random slope and intercept models were used to account for within person correlation as a result of repeated measures of hip and whole body aBMD. Linear regression was used to model changes in spine trabecular vBMD.
Among women, the annualized rate of hip aBMD loss in the highest tertile of adiponectin was −0.67% (95% CI: −0.77, −0.58) compared to −0.43% (95% CI: −0.51, −0.35)] in the lowest tertile (p trend=0.019) after adjusting for age, race, BMI, diabetes, baseline hip aBMD, and weight change. In men, hip aBMD loss was greatest in the high adiponectin group (tertile 3), however this association was not significant, p trend=0.148. After adjusting for weight change in women, the association between higher leptin and lower hip aBMD loss was attenuated and no longer significant, p trend=0.134. Leptin and adiponectin levels were not associated with whole body aBMD or trabecular lumbar spine vBMD loss.
Adiponectin was associated with increased hip aBMD loss in women only; supporting evidence that adiponectin may have an important role in bone health.
leptin; adiponectin; bone loss; hip aBMD; whole body aBMD; trabecular lumbar spine vBMD
Quantitative computed tomography (QCT) can estimate volumetric bone mineral density (vBMD) and distinguish trabecular from cortical bone. Few comprehensive studies have examined correlates of vBMD in older men. This study evaluated the impact of demographic, anthropometric, lifestyle, and medical factors on vBMD in 1172 men aged 69 to 97 years and enrolled in the Osteoporotic Fractures in Men Study (MrOS). Peripheral quantitative computed tomography (pQCT) was used to measure vBMD of the radius and tibia. The multivariable linear regression models explained up to 10% of the variance in trabecular vBMD and up to 9% of the variance in cortical vBMD. Age was not correlated with radial trabecular vBMD. Correlates associated with both cortical and trabecular vBMD were age (−), caffeine intake (−), total calcium intake (+), nontrauma fracture (−), and hypertension (+). Higher body weight was related to greater trabecular vBMD and lower cortical vBMD. Height (−), education (+), diabetes with thiazolidinedione (TZD) use (+), rheumatoid arthritis (+), using arms to stand from a chair (−), and antiandrogen use (−) were associated only with trabecular vBMD. Factors associated only with cortical vBMD included clinic site (−), androgen use (+), grip strength (+), past smoker (−), and time to complete five chair stands (−). Certain correlates of trabecular and cortical vBMD differed among older men. An ascertainment of potential risk factors associated with trabecular and cortical vBMD may lead to better understanding and preventive efforts for osteoporosis in men. © 2010 American Society for Bone and Mineral Research.
osteoporosis; vBMD; pQCT; radius; tibia
Measurement of areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) has been shown to predict fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) yields additional information about volumetric BMD (vBMD), microarchitecture, and strength that may increase understanding of fracture susceptibility. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA and trabecular and cortical vBMD and trabecular microarchitecture of the radius and tibia measured by HR-pQCT. Finite-element analysis (FEA) of HR-pQCT scans was performed to estimate bone stiffness. DXA T-scores were similar in women with and without fracture at the spine, hip, and one-third radius but lower in patients with fracture at the ultradistal radius (p <.01). At the radius fracture, patients had lower total density, cortical thickness, trabecular density, number, thickness, higher trabecular separation and network heterogeneity (p <.0001 to .04). At the tibia, total, cortical, and trabecular density and cortical and trabecular thickness were lower in fracture patients (p <.0001 to .03). The differences between groups were greater at the radius than at the tibia for inner trabecular density, number, trabecular separation, and network heterogeneity (p <.01 to .05). Stiffness was reduced in fracture patients, more markedly at the radius (41% to 44%) than at the tibia (15% to 20%). Women with fractures had reduced vBMD, microarchitectural deterioration, and decreased strength. These differences were more prominent at the radius than at the tibia. HR-pQCT and FEA measurements of peripheral sites are associated with fracture prevalence and may increase understanding of the role of microarchitectural deterioration in fracture susceptibility.
MICROARCHITECTURE; STIFFNESS; FRACTURE; OSTEOPOROSIS; POSTMENOPAUSAL
Measurement of areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) has been shown to predict fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) yields additional information about volumetric BMD (vBMD), microarchitecture, and strength that may increase understanding of fracture susceptibility. Women with (n = 68) and without (n = 101) a history of postmenopausal fragility fracture had aBMD measured by DXA and trabecular and cortical vBMD and trabecular microarchitecture of the radius and tibia measured by HR-pQCT. Finite-element analysis (FEA) of HR-pQCT scans was performed to estimate bone stiffness. DXA T-scores were similar in women with and without fracture at the spine, hip, and one-third radius but lower in patients with fracture at the ultradistal radius (p < .01). At the radius fracture, patients had lower total density, cortical thickness, trabecular density, number, thickness, higher trabecular separation and network heterogeneity (p < .0001 to .04). At the tibia, total, cortical, and trabecular density and cortical and trabecular thickness were lower in fracture patients (p < .0001 to .03). The differences between groups were greater at the radius than at the tibia for inner trabecular density, number, trabecular separation, and network heterogeneity (p < .01 to .05). Stiffness was reduced in fracture patients, more markedly at the radius (41% to 44%) than at the tibia (15% to 20%). Women with fractures had reduced vBMD, microarchitectural deterioration, and decreased strength. These differences were more prominent at the radius than at the tibia. HR-pQCT and FEA measurements of peripheral sites are associated with fracture prevalence and may increase understanding of the role of microarchitectural deterioration in fracture susceptibility. © 2010 American Society for Bone and Mineral Research.
MICROARCHITECTURE; STIFFNESS; FRACTURE; OSTEOPOROSIS; POSTMENOPAUSAL
The purpose of the present study was to determine the relationships between atherosclerotic calcified plaque (CP) and bone mineral density (BMD) in subjects with type 2 diabetes mellitus (DM2). CP in the coronary arteries, carotid bifurcation, and abdominal aorta was measured using computed tomography (CT) in 1,023 diabetic subjects from 453 families. Trabecular volumetric BMD in thoracic (T-vBMD) and lumbar (L-vBMD) spine was measured with quantitative CT (QCT), while areal BMD (aBMD) in the lumbar spine and hip was measured by dual X-ray absorptiometry (DXA). Correlation coefficients were computed to assess the magnitude of associations and generalized estimating equations (GEE1) were used to make statistical inferences while accounting for familial correlation. Subjects were 53.8% female, 85% European American (EA) and 15% African American (AA). After adjustment for age, significant inverse associations between CP and vBMD persisted in EA men (correlations between -0.11 and -0.16, all p < 0.05 with the exception of carotid CP vs. T-vBMD, p=0.076) and in AA women, excluding aortic CP, (correlations between -0.16 and -0.25, all p < 0.05). Estrogen use in AA but not EA women was consistently associated with an inverse relation between CP and vBMD. Significant inverse relationships between CP and vBMD were observed in EA men and AA women with DM2 after adjusting for age and other covariates. QCT determined vBMD was more strongly related to CP than aBMD by DXA. The relation between CP and BMD in diabetes is influenced by age, sex, and ethnicity, with further effect modification by hormone replacement therapy.
atherosclerosis; type 2 diabetes mellitus; osteoporosis; trabecular bone mineral density; calcium; computed tomography
Because they are not reliably discriminated by areal bone mineral density (aBMD) measurements, it is unclear whether minimal vertebral deformities represent early osteoporotic fractures. To address this, we compared 90 postmenopausal women with no deformity (controls) with 142 women with one or more semiquantitative grade 1 (mild) deformities and 51 women with any grade 2–3 (moderate/severe) deformities. aBMD was measured by dual-energy X-ray absorptiometry (DXA), lumbar spine volumetric bone mineral density (vBMD) and geometry by quantitative computed tomography (QCT), bone microstructure by high-resolution peripheral QCT at the radius (HRpQCT), and vertebral compressive strength and load-to-strength ratio by finite-element analysis (FEA) of lumbar spine QCT images. Compared with controls, women with grade 1 deformities had significantly worse values for many bone density, structure, and strength parameters, although deficits all were much worse for the women with grade 2–3 deformities. Likewise, these skeletal parameters were more strongly associated with moderate to severe than with mild deformities by age-adjusted logistic regression. Nonetheless, grade 1 vertebral deformities were significantly associated with four of the five main variable categories assessed: bone density (lumbar spine vBMD), bone geometry (vertebral apparent cortical thickness), bone strength (overall vertebral compressive strength by FEA), and load-to-strength ratio (45-degree forward bending ÷ vertebral compressive strength). Thus significantly impaired bone density, structure, and strength compared with controls indicate that many grade 1 deformities do represent early osteoporotic fractures, with corresponding implications for clinical decision making. © 2010 American Society for Bone and Mineral Research.
bone density; bone quality; finite-element analysis; QCT; vertebral fracture
Compared to white women, lower areal bone mineral density (aBMD) in middle-aged Vietnamese immigrants is due to reduced trabecular volumetric bone mineral density (vBMD), which in turn is associated with greater trabecular separation along with lower estrogen levels.
The epidemiology of osteoporosis in Asian populations is still poorly known, but we previously found a deficit in lumbar spine aBMD among postmenopausal Southeast Asian women, compared to white women, that persisted after correction for bone size. This issue was revisited using more sophisticated imaging techniques.
Twenty Vietnamese immigrants (age, 44–79 years) were compared to 162 same-aged white women with respect to aBMD at the hip, spine and wrist, vBMD at the hip and spine by quantitative computed tomography and vBMD and bone microstructure at the ultradistal radius by high-resolution pQCT. Bone turnover and sex steroid levels were assessed in a subset (20 Vietnamese and 40 white women).
The aBMD was lower at all sites among the Vietnamese women, but femoral neck vBMD did not differ from middle-aged white women. Significant differences in lumbar spine and ultradistal radius vBMD in the Vietnamese immigrants were due to lower trabecular vBMD, which was associated with increased trabecular separation. Bone resorption was elevated and bone formation depressed among the Vietnamese immigrants, although trends were not statistically significant. Serum estradiol was positively associated with trabecular vBMD in the Vietnamese women, but their estrogen levels were dramatically lower compared to white women.
Although reported discrepancies in aBMD among Asian women are mainly an artifact of smaller bone size, we identified a specific deficit in the trabecular bone among a sample of Vietnamese immigrants that may be related to low estrogen levels and which needs further study.
Bone mineral density; Bone structure; Bone turnover; Ethnic group; Southeast Asians
Decreased bone mineral density has been found in the chronic schizophrenic patients who have been given a long-term administration of antipsychotics. Hyperprolactinemia from the antipsychotics and the negative symptom of schizophrenia were considered as the causes for this finding. In this study, the effect of hyperprolactinemia and the negative symptom of schizophrenia on bone mineral density was investigated on male schizophrenic patients.
The cross-sectional study was carried out with the subjects of 45 male schizophrenic patients who have undertaken the monotherapy with risperidone, olanzapine and clozapine for at least one year. The demographic factors, clinical symtoms, bone mineral density and hematological test were examined for all the subjects.
No significant relationship was found between hyperprolactinemia and the decreased bone mineral density in the subjects. The negative schizophrenia symptom of the subjects showed a significant effect on the decreased bone mineral density.
The decreased bone mineral density finding in the male schizophrenic patients may be caused by the negative schizophrenia symptom rather than the hyperprolactinemia due to the antipsychotics. Additional studies are further required regarding other factors that may affect the decreased bone mineral density such as activity, calcium intake and exposure to sunlight.
Bone density; Hyperprolactinemia; Schizophrenia; Negative symptoms; Antipsychotics
Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated.
We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT). Results: FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β= −0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD.
After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight.
bone mineral density; follicle-stimulating hormone; menopausal
Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA) after completion of neoadjuvant chemotherapy.
DXA measurements of the lumbar spine (L2-4), both femora and calcanei were performed perioperatively in 46 children and adolescents (mean age: 14.3 years, range: 8.6-21.5 years). Mean Z-scores, areal BMD (g/cm2), calculated volumetric BMD (g/cm3) and bone mineral content (BMC, g) were determined.
Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to 0.18), areal BMD was 1.016 g/cm2 (95% CI: 0.950 to 1.082) and volumetric BMD was 0.330 g/cm3 (95% CI: 0.314 to 0.347) which is comparable to healthy peers. For patients with a lower extremity tumor (n = 36), the difference between the affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9) in areal BMD. The reduction of BMD was more pronounced in the calcaneus with a difference between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0) for areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA measurements were found with Spearman-rho coefficients ranging from ρ = 0.55 to ρ = 0.80.
The tumor disease located in the lower extremity in combination with offloading recommendations induced diminished BMD values, indicating local osteopenia conditions. However, the results revealed no significant decrements of lumbar spine BMD in pediatric sarcoma patients after completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into account that bone tumor patients may experience BMD decrements or secondary osteoporosis in later life. Furthermore, the peripheral assessment of BMD in the calcaneus via DXA is a feasible approach to quantify bone loss in the lower extremity in bone sarcoma patients and may serve as an alternative procedure, when the established assessment of femoral BMD is not practicable due to endoprosthetic replacements.
Coronary artery disease and osteoporosis increase in women after menopause. Computed tomography (CT) scans of the heart used to evaluate coronary arterial calcification include images of the thoracic vertebrae. The utility of using these images to assess bone health in women remains to be defined. Analyses of thoracic spine volumetric bone mineral density (vBMD) from CT scans of the heart were performed to determine how specific calibration affects the ability to assess vBMD in recently menopausal women and to evaluate how vBMD relates to areal bone mineral density (aBMD) using dual-energy X-ray absorptiometry (DEXA).
Women (n = 111) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic underwent a CT scan of the heart that included calibration phantoms and a DEXA of the lumbar spine. The Spine Cancer Assessment program was used to determine vBMD of thoracic vertebrae with and without the calibration correction.
Trabecular bone vBMD at T8 averaged 163.57 ± 28.58 and 157.94 ± 27.55 mg/cc (mean ± standard deviation, SD) for calibrated and uncalibrated values, respectively. The relationship between calibrated and uncalibrated measures approached unity (R = 0.98). Lumbar spine (L2–4) aBMD was 1.19 ± 0.16 g/cm2 (mean ± SD). Both calibrated and uncalibrated thoracic vBMD correlated positively and significantly with lumbar aBMD, but the relationship was less than unity (R =0.63).
Uncalibrated measures of thoracic spine vBMD obtained from CT scans of the heart may provide clinically relevant information about bone health and osteoporosis/osteopenia risk in recently menopausal women.
COMPUTED TOMOGRAPHY; THORACIC VERTEBRAE; LUMBAR SPINE; VOLUMETRIC BONE MINERAL DENSITY
and pathological fractures occur occasionally in children with
malignancies. This study was performed to determine the degree of
osteopenia in children with a malignancy at completion of chemotherapy.
spine (L2-L4) bone mineral density (BMD; g/cm2) and
femoral neck BMD were measured by dual energy
x ray absorptiometry in 22 children with
acute lymphoblastic leukaemia (ALL), and in 26 children with other
malignancies. Apparent volumetric density was calculated to minimise
the effect of bone size on BMD. Results were compared with those of 113 healthy controls and expressed as age and sex standardised mean Z scores.
ALL had significantly reduced lumbar volumetric (−0.77) and femoral
areal and volumetric BMDs (−1.02 and −0.98, respectively). In
patients with other malignancies, femoral areal and apparent volumetric
BMDs were significantly decreased (−0.70 and −0.78, respectively).
results demonstrate that children with a malignancy are at risk of
developing osteopenia. A follow up of BMD after the completion of
chemotherapy should facilitate the identification of patients who might
be left with impaired development of peak bone mass, and who require
specific interventions to prevent any further decrease in their
skeletal mass and to preserve their BMD.
This case-control pilot study examined whether vertebral bone mineral measures were associated with the presence of chronic low back pain (CLBP) and Modic changes (MCs), and to compare psychological wellbeing and inflammation among individuals with CLBP and MCs, compared to individuals with no history of low back pain and without MCs.
Eleven individuals with MRI-defined MCs in the lumbar spine and CLBP (cases) and 10 individuals with no history of CLBP or MCs (controls) responded to standard questionnaires regarding pain characteristics and psychological health. Bone mineral density (BMD) was measured with postero-anterior and lateral-projection dual energy X-ray absorptiometry (DXA) to estimate areal BMD (aBMD) and apparent volumetric BMD (ap.vBMD). High sensitivity serum C-reactive protein (hsCRP) was measured as an index of inflammation.
While there was no difference between the groups in measures of depression, anxiety and stress, cases reported significantly greater pain catastrophizing attitudes (P < 0.01). hsCRP concentrations did not differ between groups (P = 0.54). Among the 7 cases where MCs were identified between L3–4, significantly higher mean aBMD was observed at the affected vertebral level, compared to the adjacent, unaffected, cephalad level (P = 0.01–0.04), but not when ap.vBMD was calculated (P = 0.36).
Vertebral BMD is not reduced among individuals with CLBP and MCs compared to a control group, although pain catastrophizing attitudes are increased among individuals with CLBP and MCs.
Modic change; bone mineral density; hsCRP; psychological health
To compare microscopic magnetic resonance imaging (μMRI) parameters of trabecular micro-architecture between postmenopausal women with and without fracture who have normal or osteopenic bone mineral density (BMD) on dual-energy x-ray absorptiometry (DXA).
The study included 36 post-menopausal Caucasian women 50 years of age and older with normal or osteopenic BMD (T-scores better than −2.5 at the lumbar spine, proximal femur, and one-third radius on DXA). Eighteen women had a history of low-energy fracture, while 18 women had no history of fracture and served as an age, race, and ultra-distal radius BMD-matched control group. A three-dimensional fast large-angle spin-echo (FLASE) sequence with 137 μm × 137 μm × 400 μm resolution was performed through the non-dominant wrist of all 36 women using the same 1.5T scanner. The high resolution images were used to measure trabecular bone volume fraction, trabecular thickness, surface-to-curve ratio, and erosion index. Wilcoxon signed rank tests were used to compare differences in BMD and μMRI parameters between post-menopausal women with and without fracture.
Post-menopausal women with fracture had significantly lower (p<0.05) trabecular bone volume fraction and surface-to-curve ratio and significantly higher (p<0.05) erosion index than post-menopausal women without fracture. There was no significant difference between post-menopausal women with and without fracture in trabecular thickness (p=0.80) and BMD of the spine (p=0.21), proximal femur (p=0.19), one-third radius (p=0.47), and ultra-distal radius (p=0.90).
Post-menopausal women with normal or osteopenic BMD who had a history of low energy fracture had significantly different (p<0.05) μMRI parameters than an age, race, and ultra-distal radius BMD-matched control group of postmenopausal women with no history of fracture. Our study suggests that μMRI can be used to identify individuals without a DXA-based diagnosis of osteoporosis who have impaired trabecular micro-architecture and thus a heretofore-unappreciated elevated fracture risk.
Osteoporosis; Trabecular Micro-Architecture; Magnetic Resonance Imaging; Fracture
Background: Diminished bone mineral density (BMD) is a well known complication in women with classic galactosaemia caused by premature ovarian failure. Diminished BMD in prepubertal patients of either sex has, however, only been reported once.
Aim: To assess BMD in children with classic galactosaemia.
Methods: Eleven treated patients (five males, six females, aged 2–18 years) had BMD determined by dual energy x ray absorptiometry. Two measurements were performed, an areal measurement of the total body and a volumetric measurement of the femoral neck. Results were expressed as Z scores. Dietary calcium intake, blood calcium, phosphate, vitamin D, parathormone, and markers of bone formation (bone alkaline phosphatase, osteocalcin) and bone resorption (NTX) were determined.
Results: All patients had a significantly diminished BMD. Mean Z score of the volumetric BMD was -1.76 (range -0.7 to -3.3), and of the areal BMD -0.99 (range -0.5 to -1.4). Dietary calcium intake and calcium, phosphate, parathormone, bone alkaline phosphatase, vitamin D metabolites, and osteocalcin (free and carboxylated) were normal in all patients. NTX levels in blood were significantly lower (p < 0.001) than in control subjects.
Conclusion: BMD in this group of children of both sexes with classic galactosaemia under dietary treatment was decreased. Lower NTX levels in galactosaemics point to an apparent decreased bone resorption.
To investigate the association between hyperprolactinemia and variants of the dopamine D2 receptor (DRD2) gene in children and adolescents in long-term treatment with risperidone.
Medically healthy 7–17-year-old patients chronically treated with risperidone but receiving no other antipsychotics were selected for a cross-sectional evaluation. Four DRD2 variants were genotyped and prolactin concentration was measured. Medication history was obtained from the medical record. The effect of the TaqIA variants of the DRD2 on the risk of risperidone-induced hyperprolactinemia was the primary outcome measure.
Hyperprolactinemia was present in 50% of 107 patients (87% males) treated with risperidone for an average of 2.9 years. Age, stage of sexual development, and the dose of risperidone independently predicted a higher prolactin concentration, whereas the dose of psychostimulants was negatively correlated with it. However, these four predictors became nonsignificant when risperidone serum concentration was entered into the model. Adverse events potentially related to hyperprolactinemia were more common in participants with elevated prolactin concentration in girls (45%) compared with boys (10%). After controlling for risperidone concentration and the dose of psychostimulants, the TaqIA A1 and the A-241G alleles were associated with higher prolactin concentration, whereas the -141C Ins/Del AQ1and C957T variants had no significant effect. In addition, adverse events potentially related to hyperprolactinemia were four times more common in TaqIA A1 allele carriers.
Prolactin concentration is closely related to central DRD2 blockade, as reflected by risperidone serum concentration. Furthermore, the TaqIA and A-241G variants of the DRD2 gene could be useful in predicting the emergence of hyperprolactinemia and its potential adverse events.
adolescents; antipsychotics; children; dopamine receptors; DRD2; genetic variants; hyperprolactinemia; risperidone; TaqIA
During lactation abundant calcium is lost from the mother as a result of the amount of breast milk produced. Lactation leads to transient fragility, with some women experiencing even fragility fractures, but nearly all of these women subsequently undergo a large increase in bone mineral density (BMD), confirming that the BMD must have declined during lactation but it increases after weaning. We have retrospectively examined the relationship between the duration of breastfeeding and bone properties in Spanish premenopausal healthy women, to identify the site-specific changes in BMD.
Material and methods
Four hundred and thirty-three premenopausal healthy women, 295 with a mean of 7.82 ±6.68 months of exclusive breastfeeding and 138 control women, were studied. We examined total, trabecular and cortical volumetric BMD (mg/mm3) at the distal radius using peripheral quantitative computed tomography. Areal BMD (g/cm2) was measured using dual energy X-ray absorptiometry at the femoral neck, lumbar spine, trochanter and Ward's triangle. Phalangeal bone ultrasound was measured by amplitude-dependent speed of sound.
Areal BMD analysis at L2–L4 revealed significant intergroup differences (p < 0.05). There were significant intergroup differences in the volumetric BMD in both total and cortical bone (p < 0.05). The observed BMD of breast-feeders was higher than the BMD in non-breast-feeding women. Additionally, the lactation subgroup analysis revealed significant differences in the areal BMD at trochanter and L2–L4 (p < 0.05) and in the cortical volumetric BMD (p < 0.05).
This study adds to the growing evidence that breastfeeding has no deleterious effects and may confer an additional advantage for BMD in premenopausal women.
lactation; dual-energy X-ray absorptiometry; bone mass; ultrasonography
Hyperprolactinemia is a common endocrinological disorder that may be caused by several physiological and pathological conditions. Several drugs may determine a significant increase in prolactin serum concentration that is frequently associated with symptoms. The so-called typical antipsychotics are frequently responsible for drug-related hyperprolactinemia. Risperidone is one of the atypical neuroleptics most likely to induce hyperprolactinemia, while other atypical drugs are unfrequenlty and only transiently associated with increase of prolactin levels. Women are more sensitive than men to the hyperprolactinemic effect of antipsychotics. Classical and risperidone-induced hyperprolactinemia may be revert when a gradual antipsychotic drug discontinuation is combined with olanzapine or clozapine initiation. Antidepressant drugs with serotoninergic activity, including selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAO-I) and some tricyclics, can cause hyperprolactinemia. A long list of other compounds may determine an increase in prolactin levels, including prokinetics, opiates, estrogens, anti-androgens, anti-hypertensive drugs, H2-receptor antagonists, anti-convulsivants and cholinomimetics. Finally, hyperprolactinemia has also been documented during conditioning and after autologous blood stem-cell transplantation and during chemotherapy, even though disturbances of prolactin seem to occur less frequently than impairments of the hypothalamus-pituitary-gonad/thyroid axis after intensive treatment and blood marrow transplantation.
anti-depressants; anti-psychotics; estrogens; opioids; prokinetics; prolactin
In 100 patients with various types of endocrine dysfunction, we measured bone mineral density (BMD) at the midradius (greater than 95% cortical bone) and distal radius (75% cortical and 25% trabecular bone) by single photon absorptiometry and at the lumbar spine (greater than 66% trabecular bone) using the new technique of dual photon absorptiometry. BMD in each endocrine disorder deviated in at least one site from the sex-specific age regression of 187 normal subjects. For patients with primary hyperparathyroidism, hypercortisolism, and hyperthyroidism this deviation was negative (suggesting bone loss), whereas for patients with secondary hyperparathyroidism due to chronic renal failure, acromegaly, and postsurgical hypoparathyroidism it was positive (suggesting bone gain). When all six states of endocrine dysfunction were compared concomitantly by multivariate analysis of variance, the profile of the changes in BMD differed significantly (P less than 0.001), indicating a nonuniform response of bone to the various hormonal alterations. When values for BMD at each of the three scanning sites were compared the midradius and distal radius did not differ significantly; either of the radius measurements, however, differed significantly (P less than 0.001) from the lumbar spine. Thus, the BMD of the axial skeleton cannot be reliably predicted from measurements made in the appendicular skeleton. We conclude that the effects of endocrine dysfunction on bone density are complex and are both disease and site specific.
Osteoporosis can be a complication of ankylosing spondylitis (AS), but diagnosing spinal osteoporosis can be difficult since pathologic new bone formation interferes with the assessment of the bone mineral density (BMD). The aims of the current study were to investigate prevalence and risk factors for reduced BMD in a Swedish cohort of AS patients, and to examine how progressive ankylosis influences BMD with the use of dual-energy x-ray absorptiometry (DXA) of the lumbar spine in different projections.
Methods of assessment were questionnaires, back mobility tests, blood samples, lateral spine radiographs for syndesmophyte grading (mSASSS), DXA of the hip, radius and lumbar spine in anteroposterior (AP) and lateral projections with estimation of volumetric BMD (vBMD).
AS patients (modified New York criteria), 87 women and 117 men, mean age 50 ± 13 years and disease duration 15 ± 11 years were included. According to World Health Organization (WHO) criteria 21% osteoporosis and 44% osteopenia was diagnosed in patients > = 50 years. Under age 50 BMD below expected range for age was found in 5%. Interestingly lateral lumbar DXA showed significantly lower BMD and revealed significantly more cases with osteoporosis as compared with AP DXA. Lumbar vBMD was not different between sexes, but women had significantly more lumbar osteoporosis measured with AP DXA (P < 0.001). Men had significantly higher mSASSS (P < 0.001). Low BMD was associated with high age, disease duration, mSASSS, Bath Ankylosing Spondylitis Metrology Index (BASMI), inflammatory parameters and low body mass index (BMI). Increasing mSASSS correlated significantly with decreasing lateral and volumetric lumbar BMD, while AP lumbar BMD showed tendency to increase.
Osteoporosis and osteopenia is common in AS and associated with high disease burden. Lateral and volumetric lumbar DXA are more sensitive than AP DXA in detecting osteoporosis and are less affected by syndesmophyte formation.
Differences in osteoporotic hip fracture incidence between American whites and blacks and between women and men are considered to result, in part, from differences in bone mineral density and geometry at the femur. The aim of this study was to quantify differences in femoral bone density and geometry between a large sample of healthy American white and black women and men.
Subjects and Methods
Healthy American white (n=612) and black (n=164) premenopausal women, aged 23 to 57 years, and healthy American white (n=492) and black (n=169) men, aged 20 to 63 years, had volumetric bone mineral density (vBMD) and geometry variables measured at the femur by computerized tomography (CT), and areal bone mineral density (aBMD) at femoral neck measured by dual x-ray absorptiometry (DXA).
American blacks had higher vBMD at the femoral neck and femoral shaft cortex than American whites whereas femoral axis length and femoral neck area were not different. Men had lower vBMD at the femoral neck and femoral cortex than women but had greater femoral axis length and femoral neck area than women. The higher aBMD in American blacks than whites persisted after correction for measured area whereas the higher aBMD in men than women disappeared.
At the femoral neck, American whites have lower bone density than American blacks but similar geometry. Women have higher bone density than men in both races but have smaller geometry variables. The differences in bone density may account in part for the differences in hip fracture incidence between American blacks and whites, whereas the differences in femur size may account for the differences in hip fracture rates between men and women.
sex; race; femur; bone mineral density; geometry
A study was undertaken to observe the gains in bone mass in children and adolescents with cystic fibrosis (CF) over 24 months and to examine the relationship between areal bone mineral density (aBMD) and associated clinical parameters including physical activity, nutrition, and 25‐hydroxyvitamin D (25OHD).
Areal BMD of the total body (TB), lumbar spine (LS), and total femoral neck (FNt) were repeatedly measured in 85 subjects aged 5–18 years with CF and 100 age and sex matched controls over 2 years. At each visit anthropometric variables, nutritional parameters, pubertal status, disease severity, physical activity, dietary calcium, caloric intake, and serum 25OHD were assessed and related to aBMD.
After adjusting for age, sex, and height Z‐score, gains in LS aBMD in children (5–10 years) and TB and FNt aBMD in adolescents (11–18 years) with CF were significantly less than in controls. Lean tissue mass was significantly associated with TB and LS aBMD gains in children and adolescents and explained a significant proportion of the aBMD deficit observed. Lung function parameters were significantly associated with aBMD gains in adolescents with CF.
Inadequate bone mass accrual during childhood and adolescence contributes to the low bone mass observed in adults with CF. Accounting for the height discrepancy which is frequently observed in those with CF, in addition to age and sex, is important when assessing low bone mass in children and adolescents with CF. To optimise an individual's potential to acquire maximal bone mass, it is necessary to maximise nutritional status and limit the progression of chronic suppurative lung disease.
adolescents; bone mineral density; children; cystic fibrosis
We sought to determine the influence of single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG on volumetric bone mineral density (vBMD) and bone geometry at the radius in men. Pairwise tag SNPs (r2 ≥ 0.8) for RANKL (n = 8), RANK (n = 44), and OPG (n = 22) and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40–79 years in the European Male Ageing Study (EMAS). Here, these SNPs were analyzed in a subsample of men (n = 589) who had peripheral quantitative computed tomography (pQCT) performed at the distal (4%) and mid-shaft (50%) radius. Estimated parameters were total and trabecular vBMD (mg/mm3) and cross-sectional area (mm2) at the 4% site and cortical vBMD (mg/mm3); total, cortical, and medullary area (mm2); cortical thickness (mm); and stress strain index (SSI) (mm3) at the 50% site. We identified 12 OPG SNPs associated with vBMD and/or geometric parameters, including rs10505348 associated with total vBMD (β [95% CI] = 9.35 [2.12–16.58], P = 0.011), cortical vBMD (β [95% CI] = 5.62 [2.10–9.14], P = 0.002), cortical thickness (β [95% CI] = 0.08 [0.03–0.13], P = 0.002), and medullary area (β [95% CI] = −2.90 [−4.94 to −0.86], P = 0.005) and rs2073618 associated with cortical vBMD (β [95% CI] = −4.30 [−7.78 to −0.82], P = 0.015) and cortical thickness (β [95% CI] = −0.08 [−0.13 to −0.03], P = 0.001). Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD (β [95% CI] = −7.58 [−14.01 to −1.15], P = 0.021). There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area (β [95% CI] = 8.90 [0.92–16.88], P = 0.029). No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.
Electronic supplementary material
The online version of this article (doi:10.1007/s00223-011-9532-y) contains supplementary material, which is available to authorized users.
Osteoporosis; Genetic association; Genetic polymorphism; Male; QCT