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1.  Characterization of Low Bone Mass in Young Patients with Thalassemia by DXA, pQCT and Markers of Bone Turnover 
Bone  2011;48(6):1305-1312.
Previous reports using dual x-ray absorptiometry (DXA) suggest that up to 70% of adults with thalassemia major (Thal) have low bone mass. However, few studies have controlled for body size and pubertal delay, variables known to affect bone mass in this population. In this study, bone mineral content and areal density (BMC, aBMD) of the spine and whole body were assessed by DXA, and volumetric BMD and cortical geometries of the distal tibia by peripheral quantitative computed tomography (pQCT) in subjects with Thal (n=25, 11 male, 10 to 30 yrs) and local controls (n=34, 15 male, 7 to 30 yrs). Z-scores for bone outcomes were calculated from reference data from a large sample of healthy children and young adults. Fasting blood and urine were collected, pubertal status determined by self-assessment and dietary intake and physical activity assessed by written questionnaires. Subjects with Thal were similar in age, but had lower height, weight and lean mass index Z-scores (all p<0.001) compared to controls. DXA aBMD was significantly lower in Thal compared to controls at all sites. Adult Thal subjects (>18 yrs, n=11) had lower tibial trabecular vBMD (p=0.03), cortical area, cortical BMC, cortical thickness, periosteal circumference and section modulus Z-scores (all p<0.01) compared to controls. Cortical area, cortical BMC, cortical thickness, and periosteal circumference Z-scores (p=0.02) were significantly lower in young Thal (≤18 yrs, n=14) compared to controls. In separate multivariate models, tibial cortical area, BMC, and thickness and spine aBMD and whole body BMC Z-scores remained lower in Thal compared to controls after adjustment for gender, lean mass and/or growth deficits (all p<0.01). Tanner stage was not predictive in these models. Osteocalcin, a marker of bone formation, was significantly reduced in Thal compared to controls after adjusting for age, puberty and whole body BMC (p=0.029). In summary, we have found evidence of skeletal deficits that cannot be dismissed as an artifact of small bone size or delayed maturity alone. Given that reduced bone density and strength are associated with increased risk of fracture, therapies focused on increasing bone formation and bone size in younger patients are worthy of further evaluation.
doi:10.1016/j.bone.2011.03.765
PMCID: PMC3095710  PMID: 21443975
2.  Bone mineral density and body composition in postmenopausal women with psoriasis and psoriatic arthritis 
Introduction
The aim of the present study was to compare bone mineral density (BMD) and body composition (BC) measurements as well as identify risk factors for low BMD and osteoporotic fractures in postmenopausal women with psoriasis (Ps) and psoriatic arthritis (PsA).
Methods
A cross-sectional study was carried out in 45 PsA women, 52 Ps women and 98 healthy female controls (HC). Clinical risk factors for low bone density and osteoporotic fracture were evaluated by a specific questionnaire. An X-ray absorptiometry (DXA) at the lumbar spine, total femur and total body was performed on all patients. Skin and joint outcomes were measured by specific tools (PASI, HAQ and DAS28). Morphometric vertebral fractures were evaluated by lumbar and thoracic spine X-ray, according to Genant's method.
Results
There were no significant differences in age, body mass index (BMI), total lean mass and bone mineral density among the groups. However, the PsA group had a significantly higher body fat percentage (BF%) than the Ps and HC groups. Osteoporotic fractures were more frequently observed in PsA and Ps groups than in the HC group (P = 0.01). Recurrent falls and a longer duration of disease increased the risk of fracture (odds ratio (OR) = 18.3 and 1.08, respectively) in the PsA group (P = 0.02). Disability was the main factor related to osteoporotic fracture in the Ps group (odds ratio (OR) = 11.1) (P = 0.02).
Conclusions
Ps and PsA patients did not present lower BMD. However, they had a higher prevalence of osteoporotic fractures and higher risk of metabolic syndrome. Patients with a longer duration of disease, disability and recurrent falls need preventive measures.
doi:10.1186/ar3240
PMCID: PMC3241360  PMID: 21299865
3.  The Relationship Between Fractures and DXA Measures of BMD in the Distal Femur of Children and Adolescents With Cerebral Palsy or Muscular Dystrophy 
Children with limited or no ability to ambulate frequently sustain fragility fractures. Joint contractures, scoliosis, hip dysplasia, and metallic implants often prevent reliable measures of bone mineral density (BMD) in the proximal femur and lumbar spine, where BMD is commonly measured. Further, the relevance of lumbar spine BMD to fracture risk in this population is questionable. In an effort to obtain bone density measures that are both technically feasible and clinically relevant, a technique was developed involving dual-energy X-ray absorptiometry (DXA) measures of the distal femur projected in the lateral plane. The purpose of this study is to test the hypothesis that these new measures of BMD correlate with fractures in children with limited or no ability to ambulate. The relationship between distal femur BMD Z-scores and fracture history was assessed in a cross-sectional study of 619 children aged 6 to 18 years with muscular dystrophy or moderate to severe cerebral palsy compiled from eight centers. There was a strong correlation between fracture history and BMD Z-scores in the distal femur; 35% to 42% of those with BMD Z-scores less than −5 had fractured compared with 13% to 15% of those with BMD Z-scores greater than −1. Risk ratios were 1.06 to 1.15 (95% confidence interval 1.04–1.22), meaning a 6% to 15% increased risk of fracture with each 1.0 decrease in BMD Z-score. In clinical practice, DXA measure of BMD in the distal femur is the technique of choice for the assessment of children with impaired mobility. © 2010 American Society for Bone and Mineral Research
doi:10.1359/jbmr.091007
PMCID: PMC3153393  PMID: 19821773
Fractures; Osteopenia; Children; Bone Density; Disabilities
4.  Diffuse idiopathic skeletal hyperostosis (DISH): relation to vertebral fractures and bone density 
Osteoporosis International  2010;22(6):1789-1797.
Summary
Radiographs and spinal bone mineral density (BMD) were evaluated from 342 elderly men regarding possible effects of diffuse idiopathic skeletal hyperostosis (DISH) on vertebral fractures and densitometry measurements. Prevalent vertebral fractures were more frequent among men with DISH compared to men with no DISH even after fracture prevalence was adjusted for BMD. Paravertebral calcifications should be considered in patients with DISH when interpreting BMD measurements because both dual X-ray absorptiometry (DXA) and quantitative CT (QCT) densitometry may not be reliable.
Introduction
The purpose of this study is to evaluate the prevalence of DISH in older men and its association with vertebral fractures and with BMD determined by DXA and QCT.
Methods
Lateral radiographs of the spine were analyzed in a sample of 342 men aged ≥65 years participating in the MrOS Study concerning the presence and grade of DISH and vertebral fractures. Lumbar BMD was measured by both DXA (areal, grams per square centimeter) and QCT (volumetric, grams per cubic centimeter). The association between DISH, BMD, and presence of fractures was studied using χ2 and t tests.
Results
DISH was present in 52% (178/342) of the men. Men with DISH were older (mean, 75.1 vs 73.3, p < 0.05) and more likely to have prevalent fractures (28% vs 20%, p < p = 0.09). BMD assessed with DXA (1.08 vs 1.00 g/cm2, p ≤ 0.0001), but not with QCT (0.11 vs 0.11 g/cm3, p = 0.65), was significantly higher in men with DISH compared to men without DISH. Significantly lower BMD of men with both DISH and fractures compared to men with DISH but without fractures was only detected by QCT (−25%, 0.09 vs 0.12, p < 0.05). Both DXA BMD and QCT BMD were significantly higher in severe lumbar DISH (+22% and +31%, p < 0.0001), respectively.
Conclusion
DISH was associated with a higher prevalence of vertebral fractures in elderly men. Lumbar ossifications related to DISH should be considered when interpreting BMD measurements to predict their fracture risk.
doi:10.1007/s00198-010-1409-9
PMCID: PMC3092929  PMID: 20882271
DISH; DXA; MrOS; QCT; Vertebral fracture
5.  Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. 
Annals of the Rheumatic Diseases  1995;54(10):801-806.
OBJECTIVES--To determine the prevalence of vertebral fracture in postmenopausal women with steroid treated rheumatoid arthritis (RA), and whether the risk of vertebral fracture could be predicted from measurements of bone mineral density (BMD). METHODS--Vertebral deformities were defined from spine radiographs in 76 postmenopausal women with steroid treated RA (aged 50-79 years) and 347 age matched women from a population based group, using a morphometric technique. Lumbar spine (LS) BMD was measured by dual energy x ray absorptiometry. RESULTS--The odds ratio for vertebral fracture in the women with RA was 6.2 (95% confidence interval 3.2 to 12.3). The decrease in LS-BMD was less than expected for the observed prevalence of vertebral fracture and, among the women with RA, LS-BMD was not lower in those with vertebral fractures. CONCLUSIONS--We conclude that patients with steroid treated RA may have abnormal bone quality, and that LS-BMD cannot be used to predict the risk of vertebral fracture in these patients.
PMCID: PMC1010013  PMID: 7492217
6.  Vertebral Bone Mineral Measures and Psychological Wellbeing Among Individuals with Modic Changes 
Purpose
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.4137/CCRep.S9209
PMCID: PMC3320114  PMID: 22493564
Modic change; bone mineral density; hsCRP; psychological health
7.  Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassemia syndromes in North America 
British journal of haematology  2009;146(5):546-556.
Objective
To determine differences in the rates of growth, endocrine and calcium related abnormalities in the various thalassemia syndromes in North America with current therapy.
Methods
Medical history, physical examinations and blood and urine collections were obtained from patients with all thalassemia syndromes age 6 years and older in the Thalassemia Clinical Research Network.
Results
361 subjects, 49% male, mean age 23.2 years (range 6.1 to 75 years) were studied. Approximately 25% of children and adults, regardless of the thalassemia syndrome, had short stature. Overall growth in children was mildly affected. Final height was close to midparental height (z = -0.73 ± 1.24). Patients with beta thalassemia major (TM) had higher rates of hypogonadism, multiple endocrinopathies, worse hyperglycemia, subclinical hypoparathyroidism and hypercalciuria. Hypogonadism remained the most frequent endocrinopathy and was frequently under-treated. 12.8% of the subjects had 25 vitamin D concentrations less than 27nmol/L and 82% less than 75nmol/L, regardless of the thalassemia syndrome. Adolescents had lower 25 vitamin D levels than children and adults.
Conclusions
Compared to patients with other thalassemia syndromes, those with beta TM suffer from higher rates of multiple endocrinopathies, abnormal calcium metabolism and hypercalciuria. Vitamin D abnormalities are high among adolescents.
doi:10.1111/j.1365-2141.2009.07793.x
PMCID: PMC2798591  PMID: 19604241
8.  Evaluation of Trabecular Micro-Architecture in Non-Osteoporotic Post-Menopausal Women With and Without Fracture 
Journal of Bone and Mineral Research  2012;27(7):1494-1500.
Purpose
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).
Methods
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.
Results
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).
Conclusions
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.
doi:10.1002/jbmr.1595
PMCID: PMC3377771  PMID: 22407970
Osteoporosis; Trabecular Micro-Architecture; Magnetic Resonance Imaging; Fracture
9.  Bone Mineral Content and Bone Mineral Density Are Lower in Older than in Younger Females with Rett Syndrome 
Pediatric research  2008;64(4):435-439.
Although bone mineral deficits have been identified in Rett syndrome (RTT), the prevalence of low bone mineral density and its association with skeletal fractures and scoliosis has not been characterized fully in girls and women with RTT. Accordingly, we measured total body bone mineral content (BMC) and bone mineral density (BMD) using dual energy x-ray absorptiometry in a cross-sectional group of 50 females, ages 2-38 y, with RTT. Methyl-CpG-binding 2 (MECP2) mutations, skeletal fractures, and scoliosis were documented. The prevalence of BMC and BMD z-scores <-2 SD was 59% and 45%, respectively. Although absolute BMC and BMD increased significantly with increasing age, BMC and BMD z-scores were significantly lower in older than in younger females. The prevalence of fractures and scoliosis was 28% and 64%, respectively. Low BMD z-scores were positively associated with fractures and scoliosis. Deficits in BMD were identified across a broad range of MECP2 mutations. This study identified associations among low bone mineral density, fractures, and scoliosis, and underscored the need for better understanding of the molecular mechanisms of MECP2 in the regulation of bone mineral metabolism.
doi:10.1203/PDR.0b013e318180ebcd
PMCID: PMC2663405  PMID: 18535484
bone mineral density; skeletal fractures; scoliosis; genotype-phenotype correlations; body composition; anticonvulsants
10.  Children with Spina Bifida are at Risk for Low Bone Density 
Background
Patients with spina bifida frequently sustain lower extremity fractures which may be difficult to diagnose because they feel little or no pain, although the relative contributions of low bone density to pain insensitivity are unclear. Routine dual-energy xray absorptiometry (DXA) scanning is unreliable because these patients lack bony elements in the spine, and many have joint contractures and/or implanted hardware.
Questions/purposes
We asked (1) if the lateral distal femoral scan is useful in spina bifida; (2) whether nonambulatory children with spina bifida exhibit differences in bone mineral density (BMD) compared with an age-and-sex-matched population; and (3) whether Z-scores were related to extremity fracture incidence.
Methods
We retrospectively reviewed 37 patients with spina bifida who had DXA scans and sufficient data. Z-scores were correlated with functional level, ambulatory status, body mass index, and fracture history.
Results
The distal femoral scan could be performed in subjects for whom total body and/or lumbar scans could not be performed accurately. Twenty-four of 37 had Z-scores below −2 SD, defined as “low bone density for age.” Ten of 35 patients (29%) with fracture information had experienced one or more fractures. Our sample size was too small to correlate Z-score with fracture.
Conclusion
We believe BMD should be monitored in patients with spina bifida; nonambulatory patients with spina bifida and those with other risk factors are more likely to have low bone density for age than unaffected individuals. The LDF scan was useful in this population in whom lumbar and total body scans are often invalidated by contracture or artifact. Although lower extremity fractures occur regardless of ambulation or bone density, knowing an individual’s bone health status may lead to interventions to improve bone health.
doi:10.1007/s11999-010-1634-8
PMCID: PMC3069300  PMID: 21042897
11.  The effect of whole body vibration therapy on bone density in patients with thalassemia: A pilot study 
American journal of hematology  2012;87(10):10.1002/ajh.23305.
Patients with thalassemia (Thal) have low bone mass which can lead to fracture and decreased quality of life. There are no noninvasive anabolic therapies available to improve bone health in Thal. A longitudinal cross-over pilot trial was conducted to evaluate the effectiveness of low magnitude whole body vibration (WBV) therapy on bone in 18 patients with Thal (9 adults, 10 male, 22.1 ± 10.7 years). Subjects were asked to stand on a vibrating platform (30 Hz, 0.3 g) for 20 min/day for 6 months. Areal bone mineral density (aBMD) by DXA and volumetric BMD by peripheral quantitative computed tomography (pQCT) was assessed at baseline, 6 and 12 months. Adherence in the first 3 months was greater when compared with the second 3 months (14 ± 6 vs. 10 ± 7 min/day, P=0.007). Intention to treat analysis revealed a significant increase in whole body BMC (2.6%; P = 0.021), BMC/Ht (2.6%, P = 0.02) and aBMD (1.3%; P = 0.036), as well as a net increase in serum markers of bone formation (Osteocalcin/CTx, P = 0.027) in the adult subjects. These preliminary findings suggest that vibration therapy may be an effective nonpharmacologic intervention in Thal. Future research is needed to confirm these findings in a larger sample for longer duration.
doi:10.1002/ajh.23305
PMCID: PMC3845963  PMID: 22886910
12.  Eleven years of experience with bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I 
We report the 11-year follow-up of a man with osteogenesis imperfecta type I who was treated with bisphosphonates and alfacalcidol. A 36-year-old Japanese man with osteogenesis imperfecta type I who had frequently experienced painful fragility fractures consulted our clinic because of chronic back pain. The patient had multiple morphometric vertebral fractures and a low bone mineral density (BMD) at the lumbar spine. The patient was treated with cyclical etidronate 200 mg, for 2 weeks every 3 months, plus alfacalcidol 1 μg daily, for 2 years; and alendronate 5 mg daily or 35 mg weekly, plus alfacalcidol 1 μg daily for 9 years. After 11 years of treatment, BMD at the lumbar spine increased by 6.4%, following a 20.3% reduction in serum alkaline phosphatase. Serum calcium, phosphorus, and intact parathyroid hormone levels remained within the normal ranges. Three clinical fractures occurred at two ribs and the metacarpus, and two morphometric vertebral fractures occurred at the thoracic spine during the 11-year treatment period, but the patient experienced no adverse effects. Thus, the present case report shows the long-term outcome and safety of bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I.
doi:10.2147/TCRM.S38404
PMCID: PMC3534324  PMID: 23293527
etidronate; alendronate; fragility fracture; bone mineral density; osteogenesis imperfecta
13.  Factors associated with low bone mass in the hemodialysis patients – a cross-sectional correlation study 
Background
Low bone mass is common in end-stage renal disease patients, especially those undergoing hemodialysis. It can lead to serious bone health problems such as fragility fractures. The purpose of this study is to investigate the risk factors of low bone mass in the hemodialysis patients.
Methods
Sixty-three subjects on hemodialysis for at least 6 months were recruited from a single center for this cross-sectional study. We collected data by questionnaire survey and medical records review. All subjects underwent a bone mineral density (BMD) assay with dual-energy x-ray absorptiometry at the lumbar spine and right hip. Data were statistically analyzed by means of descriptive analysis, independent t test and one way analysis of variance for continuous variables, Pearson product-moment correlation to explore the correlated factors of BMD, and stepwise multiple linear regression to identify the predictors of low bone mass.
Results
Using WHO criteria as a cutoff point, fifty-one subjects (81%) had a T-score lower than -1, of them 8 subjects (13%) had osteoporosis with the femoral neck most commonly affected. Regarding risk factors, age, serum alkaline phosphatase (ALP) level, and intact parathyroid hormone (iPTH) level had significant negative correlations with the femoral neck and lumbar spine BMD. On the other hand, serum albumin level, effective exercise time, and body weight (BW) had significant positive correlations with the femoral neck and lumbar spine BMD. Age, effective exercise time, and serum albumin level significantly predicted the femoral neck BMD (R2 × 0.25), whereas BW and the ALP level significantly predicted the lumbar spine BMD (R2 × 0.20).
Conclusion
This study showed that advanced age, low BW, low serum albumin level, and high ALP and iPTH levels were associated with a low bone mass in the hemodialysis patients. We suggest that regular monitoring of the femoral neck BMD, maintaining an adequate serum albumin level and BW, and undertaking an exercise program are important to improve bone health in the patients undergoing hemodialysis.
doi:10.1186/1471-2474-10-60
PMCID: PMC2700075  PMID: 19497099
14.  Bone Mineral Density, Bone Turnover Markers and Fractures in Patients with Systemic Sclerosis: A Case Control Study 
PLoS ONE  2013;8(6):e66991.
Objective
The aim of our study was to elucidate the pathophysiology of systemic sclerosis-related osteoporosis and the prevalence of vertebral fragility fracture in postmenopausal women with systemic sclerosis (SSc).
Methodology
Fifty-four postmenopausal women with scleroderma and 54 postmenopausal controls matched for age, BMI, and smoking habits were studied. BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline. All subjects had a spine X-ray to ascertain the presence of vertebral fractures.
Results
bone mineral density at lumbar spine (BMD 0.78±0.08 vs 0.88±0.07; p<0,001), femoral neck (BMD: 0.56±0.04 vs 0.72±0.07; p<0,001) and total femur (BMD: 0.57±0.04 vs 0.71±0.06; p<0,001) and ultrasound parameter at calcaneus (SI: 80.10±5.10 vs 94.80±6.10 p<0,001) were significantly lower in scleroderma compared with controls; bone turnover markers and parathyroid hormone level were significantly higher in scleroderma compared with controls, while serum of 25(OH)D3 was significantly lower. In scleroderma group the serum levels of 25(OH)D3 significantly correlated with PTH levels, BMD, stiffness index and bone turnover markers. One or more moderate or severe vertebral fractures were found in 13 patients with scleroderma, wherease in control group only one patient had a mild vertebral fracture.
Conclusion
Our data shows, for the first time, that vertebral fractures are frequent in subjects with scleroderma, and suggest that lower levels of 25(OH)D3 may play a role in the risk of osteoporosis and vertebral fractures.
doi:10.1371/journal.pone.0066991
PMCID: PMC3688576  PMID: 23818972
15.  Dual energy X-ray absorptiometry: Pitfalls in measurement and interpretation of bone mineral density 
Osteoporosis is common disorder of elderly population all over the world as well as in India. The presence of osteoporosis predicts fracture risk. Fragility fracture has marked morbidity as well as mortality. Thus, osteoporosis has marked therapeutic and economic implications. Osteoporosis is defined by low bone mineral density (BMD). The gold-standard method to assess BMD is dual X-ray absorptiometry (DXA). In India, hologic and lunar machines are most commonly used to measure BMD; these machines have their own normative data from which patients BMD is compared and results are generated. As per recommendations, all postmenopausal women and men above 70 years need BMD estimation other than quite a few other specific indications as well. With increasing life expectancy, increased awareness of osteoporosis, and availability of DXA machines, there is flooding of requests for BMD estimation. In view of all this, it becomes imperative on part of physicians, orthopedicians, rheumatologists, and endocrinologists alike to be fully aware about pitfalls in BMD assessment by DXA and interpretation of BMD reports.
doi:10.4103/2230-8210.109659
PMCID: PMC3683192  PMID: 23776890
Bone mineral density; dual energy x-ray absorptiometry; osteoporosis; osteopenia
16.  No association between the aluminium content of trabecular bone and bone density, mass or size of the proximal femur in elderly men and women 
Background
Aluminium is considered a bone toxic metal since poisoning can lead to aluminium-induced bone disease in patients with chronic renal failure. Healthy subjects with normal renal function retain 4% of the aluminium consumed. They might thus also accumulate aluminium and eventually be at risk of long-term low-grade aluminium intoxication that can affect bone health.
Methods
We therefore examined 62 patients with femoral neck fractures or osteoarthritis of the hip (age range 38–93), with the aim of examining whether aluminium in bone is associated with bone-mineral density (BMD), content (BMC) or width of the femoral neck measured by dual-energy X-ray absorptiometry (DXA). During operations bone biopsies were taken from the trabecular bone of the proximal femur. The samples were measured for their content of aluminium using a mass spectrometer.
Results
No significant association between the aluminium content in bone and femoral neck BMD, BMC or width could be found after multivariate adjustment.
Conclusion
Our results indicate that the accumulated aluminium content in bone during life does not substantially influence the extent of osteoporosis.
doi:10.1186/1471-2474-7-69
PMCID: PMC1560132  PMID: 16928265
17.  Severity of aortic calcification is positively associated with vertebral fracture in older men—a densitometry study in the STRAMBO cohort 
Summary
In older men, severe abdominal aortic calcification and vertebral fracture (both assessed using dual-energy X-ray absorptiometry) were positively associated after adjustment for confounders including bone mineral density.
Introduction
Abdominal aortic calcification (AAC) is associated with higher fracture risk, independently of low bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) can be used to assess both vertebral fracture and AAC and requires less time, cost, and radiation exposure.
Methods
We conducted a cross-sectional study of the association between AAC and prevalent vertebral fractures in 901 men ≥50 years old. We used DXA (vertebral fracture assessment) to evaluate BMD, vertebral fracture, and AAC.
Results
Prevalence of vertebral fracture was 11 %. Median AAC score was 1 and 12 % of men had AAC score >6. After adjustment for age, weight, femoral neck BMD, smoking, ischemic heart disease, diabetes, and hypertension, AAC score >6 (vs ≤6) was associated with 2.5 (95 % CI, 1.4–4.5) higher odds of vertebral fracture. Odds of vertebral fracture for AAC score >6 increased with vertebral fracture severity (grade 1, OR=1.8; grade 2, OR=2.4; grade 3, OR=4.4; trend p<0.01) and with the number of vertebral fractures (1 fracture, OR=2.0, >1 fracture, OR=3.5). Prevalence of vertebral fracture was twice as high in men having both a T-score<−2.0 and an AAC score>6 compared with men having only one of these characteristics.
Conclusions
Men with greater severity AAC had greater severity and greater number of vertebral fractures, independently of BMD and co-morbidities. DXA can be used to assess vertebral fracture and AAC. It can provide a rapid, safe, and less expensive alternative to radiography. DXA may be an important clinical tool to identify men at high risk of adverse outcomes from osteoporosis and cardiovascular disease.
doi:10.1007/s00198-012-2101-z
PMCID: PMC3656471  PMID: 22872071
Aortic calcification; DXA; Men; Vertebral fracture; Vertebral fracture assessment
18.  How reliable is a radiological report in osteoporosis in diagnosing low bone density? 
The Ulster Medical Journal  2003;72(1):34-37.
Patients are often referred to osteoporosis clinics with a radiological diagnosis of osteoporosis. Previous studies attempting to ascertain risk of osteoporosis from radiographs have been conflicting. The aim of our study was to determine how reliable spinal radiographs were at detecting low bone density compared with Dual Energy X ray Absorptiometry (DXA). We retrospectively measured the Bone Mineral Density (BMD) at the spine in 130 patients with a radiological diagnosis of osteopenia or osteoporosis in the absence of vertebral fractures. They were compared with a group of 119 age and sex matched patients with one or more low trauma vertebral fractures. There was a statistically significant difference in the mean BMD between these two groups. 12.7%, of the x-ray group with osteopenia reported, had a normal bone density, 49.2% had osteopenia (T-score -1 to -2.5) and 38.1% had osteoporosis (T-score <-2.5). Of those with a radiological report of osteoporosis, 12.8% had a normal bone density, 44.7% had osteopenia and 42.6% had osteoporosis. We conclude that a radiological report of low bone density is a strong predictor of osteopenia or osteoporosis by BMD measurement.
PMCID: PMC2475391  PMID: 12868701
19.  Effect of fat on measurement of bone mineral density 
Objective
To determine if increasing fatness interferes with the measurement of fat and bone mineral density (BMD) by dual-energy X-ray absorptiometry (Lunar iDXA).
Methods
We performed measurements of BMD and fat on a section of a beef femur defatted by prolonged boiling in detergent, completely surrounded by increasing thicknesses of lard. Initially the bone was placed in the marked spine area, overlying a 6L plastic bottle which was placed in the marked trunk area of the iDXA. The plastic bottle was then removed and further measurements were carried out with increasing thicknesses of lard surrounding the bone. Measurements were repeated 4 times.
Results
The reported measurement of BMD progressively increased with each increased layer of lard surrounding the bone. All the iDXA BMD measurements were significantly (P<0.01) different from one another. When surrounded by 3 layers of lard the reported BMD was 20.5% greater than the reported BMD when the bone was not surrounded by any lard. The differences between the actual amount of fat measured by chemical analysis and weighing, and the reported measurement of fat by iDXA were significant with all 3 thicknesses of lard (P<0.01); the percentage difference between the fat measured by iDXA and that measured chemically decreased as the number of layers of lard increased.
Conclusion
We found that iDXA overestimated fat by up to 11.1%. The percentage overestimation of fat diminished as the amount of fat increased. BMD was overestimated by 20.5% when surrounded by 3 layers of fat compared to when there was no surrounding fat. In contrast to fat, the percentage overestimation of BMD increased as increasing amounts of fat surrounding the bone Using earlier generation DXAs, others have reported that measurements were ± 20–50% inaccurate and differed according to the configuration of the phantoms. The measurement of BMD and fat is the main clinical purpose of iDXA; the present experiment has shown that there are substantial inaccuracies in the measurement of BMD and fat. It is not known how these inaccuracies compare with those of earlier generations of DXA machines.
PMCID: PMC3035852  PMID: 21318078
20.  Relationship between Chronic Transfusion Therapy and Body Composition in Subjects with Thalassemia 
The Journal of pediatrics  2010;157(4):641-647.e2.
Objective
To measure body composition in patients with thalassemia and explore its relationship to abnormal growth and bone mass.
Study design
Cross-sectional, multi-center study. Fat, lean, and bone mineral density (BMD) were assessed by DXA. Medical history, food frequency and physical activity questionnaires were conducted in 257 transfused thalassemia patients (23.7 ± 11 yr, Mean±SD, 51% male) compared with 113 non-transfused patients (21.3 ± 13 yr, 44% male).
Results
Subjects with thalassemia were leaner compared with healthy Americans from NHANES III data. Transfused subjects had higher percentage body fat compared with non- transfused after controlling for age, sex and ethnicity; 11.8% of non-transfused pediatric subjects were considered underweight, significantly lower than NHANES data (p=0.03). Hemoglobin level was positively related to lean mass (p=0.008). Body fat and lean mass were positive predictors for both height and BMD Z-scores after adjustment for transfusion status, age, sex, ethnicity, calcium intake and physical activity (all p<0.001).
Conclusions
Though the majority of adult patients with thalassemia had healthy body composition with rare obesity, young, non-transfused patients appear at risk for being underweight. Optimizing physical activity and appropriate use of transfusion therapy may improve growth and bone health in these at risk patients.
doi:10.1016/j.jpeds.2010.04.064
PMCID: PMC2936667  PMID: 20547400
DXA; lean mass; fat mass; body mass index (BMI); calcium
21.  Bone microarchitecture in ankylosing spondylitis and the association with bone mineral density, fractures, and syndesmophytes 
Arthritis Research & Therapy  2013;15(6):R179.
Introduction
Osteoporosis of the axial skeleton is a known complication of ankylosing spondylitis (AS), but bone loss affecting the peripheral skeleton is less studied. This study on volumetric bone mineral density (vBMD) and bone microarchitecture in AS was conducted to compare peripheral vBMD in AS patients with that in healthy controls, to study vBMD in axial compared with peripheral bone, and to explore the relation between vertebral fractures, spinal osteoproliferation, and peripheral bone microarchitecture and density.
Methods
High-resolution peripheral quantitative computed tomography (HRpQCT) of ultradistal radius and tibia and QCT and dual-energy x-ray absorptiometry (DXA) of lumbar spine were performed in 69 male AS patients (NY criteria). Spinal radiographs were assessed for vertebral fractures and syndesmophyte formation (mSASSS). The HRpQCT measurements were compared with the measurements of healthy controls.
Results
The AS patients had lower cortical vBMD in radius (P = 0.004) and lower trabecular vBMD in tibia (P = 0.033), than did the controls. Strong correlations were found between trabecular vBMD in lumbar spine, radius (rS = 0.762; P < 0.001), and tibia (rS = 0.712; P < 0.001).
When compared with age-matched AS controls, patients with vertebral fractures had lower lumbar cortical vBMD (-22%; P = 0.019), lower cortical cross-sectional area in radius (-28.3%; P = 0.001) and tibia (-24.0%; P = 0.013), and thinner cortical bone in radius (-28.3%; P = 0.001) and tibia (-26.9%; P = 0.016).
mSASSS correlated negatively with trabecular vBMD in lumbar spine (rS = -0.620; P < 0.001), radius (rS = -0.400; p = 0.001) and tibia (rS = -0.475; p < 0.001) and also with trabecular thickness in radius (rS = -0.528; P < 0.001) and tibia (rS = -0.488; P < 0.001).
Adjusted for age, syndesmophytes were significantly associated with decreasing trabecular vBMD, but increasing cortical vBMD in lumbar spine, but not with increasing cortical thickness or density in peripheral bone. Estimated lumbar vBMD by DXA correlated with trabecular vBMD measured by QCT (rS = 0.636; P < 0.001).
Conclusions
Lumbar osteoporosis, syndesmophytes, and vertebral fractures were associated with both lower vBMD and deteriorated microarchitecture in peripheral bone. The results indicate that trabecular bone loss is general, whereas osteoproliferation is local in AS.
doi:10.1186/ar4368
PMCID: PMC3978766  PMID: 24517240
22.  Reduced hip bone mineral density is related to physical fitness and leg lean mass in ambulatory individuals with chronic stroke 
Following a stroke, reduced level of physical activity and functional use of the paretic leg may lead to bone loss and muscle atrophy. These factors and the high incidence of falls may contribute to hip fractures in the stroke population. This study was the first to examine total proximal femur bone mineral content (BMC) and bone mineral density (BMD) and their relationship to stroke-specific impairments in ambulatory individuals with chronic stroke (onset >1 year). We utilized dual-energy X-ray absorptiometry (DXA) to acquire proximal femur and total body scans on 58 (23 women) community-dwelling individuals with chronic stroke. We report total proximal femur BMC (g) and BMD (g/cm2) derived from the proximal femur scans, and lean mass (g) and fat mass (g) for each leg derived from the total body scans. Each subject was evaluated for ambulatory capacity (Six Minute Walk Test), knee extension strength (hand-held dynamometry), physical fitness [Maximal oxygen uptake (VO2max)], and spasticity (Modified Ashworth Scale). Results showed that the paretic leg had significantly lower proximal femur BMD, lean mass, and percent lean mass but higher fat mass than the non-paretic leg for both men and women. Proximal femur BMD of the paretic leg was significantly related to ambulatory capacity (r=0.33, p=0.011), muscle strength (r=0.39, p=0.002), physical fitness (r=0.57, p<0.001) but not related to spasticity (r=−0.23, p=0.080). Multiple regression analysis showed that lean mass in the paretic leg was a major predictor (R2=0.371, p<0.001) of the paretic proximal femur BMD. VO2max was a significant predictor of both paretic proximal femur BMD (R2=0.325, p<0.001) and lean mass in the paretic leg (R2=0.700, p<0.001). Further study is required to determine whether increasing physical fitness and lean mass is important to improve hip bone health in chronic stroke.
doi:10.1007/s00198-005-1925-1
PMCID: PMC3145668  PMID: 15902416 CAMSID: cams1841
Aerobic capacity; cerebrovascular accident; osteoporosis; physical activity; rehabilitation
23.  Normative Data for Bone Mass in Healthy Term Infants from Birth to 1 Year of Age 
Journal of Osteoporosis  2012;2012:672403.
For over 2 decades, dual-energy X-ray absorptiometry (DXA) has been the gold standard for estimating bone mineral density (BMD) and facture risk in adults. More recently DXA has been used to evaluate BMD in pediatrics. However, BMD is usually assessed against reference data for which none currently exists in infancy. A prospective study was conducted to assess bone mass of term infants (37 to 42 weeks of gestation), weight appropriate for gestational age, and born to healthy mothers. The group consisted of 33 boys and 26 girls recruited from the Winnipeg Health Sciences Center (Manitoba, Canada). Whole body (WB) as well as regional sites of the lumbar spine (LS 1–4) and femur was measured using DXA (QDR 4500A, Hologic Inc.) providing bone mineral content (BMC) for all sites and BMD for spine. During the year, WB BMC increased by 200% (76.0 ± 14.2 versus 227.0 ± 29.7 g), spine BMC by 130% (2.35 ± 0.42 versus 5.37 ± 1.02 g), and femur BMC by 190% (2.94 ± 0.54 versus 8.50 ± 1.84 g). Spine BMD increased by 14% (0.266 ± 0.044 versus 0.304 ± 0.044 g/cm2) during the year. This data, representing the accretion of bone mass during the first year of life, is based on a representative sample of infants and will aid in the interpretation of diagnostic DXA scans by researchers and health professionals.
doi:10.1155/2012/672403
PMCID: PMC3468026  PMID: 23091773
24.  Contribution of Serum Inflammatory Markers to Changes in Bone Mineral Content and Density in Postmenopausal Women: A 1-Year Investigation 
Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content and density (BMC, BMD) and determined the contribution of inflammatory markers to 1-year changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss (SIRBL) project who were randomly assigned to one of three treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy x-ray absorptiometry (DXA) and the 4% distal tibia (DT) by peripheral quantitative computed tomography (pQCT). Serum inflammatory markers (C-reactive protein (CRP), interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and white blood cell count (WBC)) were measured at baseline, 6 and 12 months. Due to attrition or missing values, data analysis at 12 months includes only 235 women. Significant associations among Il-6, TNF-α, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1% to 6.1% of the variance to the observed 12 month changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss.
doi:10.1016/j.jocd.2010.04.003
PMCID: PMC2912969  PMID: 20605499
Cytokines; Bone mineral content and density (BMC, BMD); Inflammatory markers; Postmenopausal women
25.  Assessment of volumetric bone mineral density of the femoral neck in postmenopausal women with and without vertebral fractures using quantitative multi-slice CT 
Objective: To demonstrate the validity and reliability of volumetric quantitative computed tomography (vQCT) with multi-slice computed tomography (MSCT) and dual energy X-ray absorptiometry (DXA) for hip bone mineral density (BMD) measurements, and to compare the differences between the two techniques in discriminating postmenopausal women with osteoporosis-related vertebral fractures from those without. Methods: Ninety subjects were enrolled and divided into three groups based on the BMD values of the lumbar spine and/or the femoral neck by DXA. Groups 1 and 2 consisted of postmenopausal women with BMD changes <−2SD, with and without radiographically confirmed vertebral fracture (n=11 and 33, respectively). Group 3 comprised normal controls with BMD changes ≥−1SD (n=46). Post-MSCT (GE, LightSpeed16) scan reconstructed images of the abdominal-pelvic region, 1.25 mm thick per slice, were processed by OsteoCAD software to calculate the following parameters: volumetric BMD values of trabecular bone (TRAB), cortical bone (CORT), and integral bone (INTGL) of the left femoral neck, femoral neck axis length (NAL), and minimum cross-section area (mCSA). DXA BMD measurements of the lumbar spine (AP-SPINE) and the left femoral neck (NECK) also were performed for each subject. Results: The values of all seven parameters were significantly lower in subjects of Groups 1 and 2 than in normal postmenopausal women (P<0.05, respectively). Comparing Groups 1 and 2, 3D-TRAB and 3D-INTGL were significantly lower in postmenopausal women with vertebral fracture(s) [(109.8±9.61) and (243.3±33.0) mg/cm3, respectively] than in those without [(148.9±7.47) and (285.4±17.8) mg/cm3, respectively] (P<0.05, respectively), but no significant differences were evident in AP-SPINE or NECK BMD. Conclusion: the femoral neck-derived volumetric BMD parameters using vQCT appeared better than the DXA-derived ones in discriminating osteoporotic postmenopausal women with vertebral fractures from those without. vQCT might be useful to evaluate the effect of osteoporotic vertebral fracture status on changes in bone mass in the femoral neck.
doi:10.1631/jzus.B0820409
PMCID: PMC2704967  PMID: 19585667
Osteoporosis; Bone mineral density (BMD); Volumetric QCT; Hip fracture; Postmenopausal women

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