Stephanie A. Atkinson

2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary

See related commentary by Kanis, page [1829][1] Since the publication of the Osteoporosis Canada guidelines in 2002, there has been a paradigm shift in the prevention and treatment of osteoporosis and fractures. [1][2],[2][3] The focus now is on preventing fragility fractures and their negative

Serum levels of perfluoroalkyl compounds in human maternal and umbilical cord blood samples

Perfluoroalkyl compounds (PFCs) are end-stage metabolic products from industrial flourochemicals used in the manufacture of plastics, textiles, and electronics that are widely distributed in the environment. The objective of the present study was to quantify exposure to perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonate (PFHxS), perfluoroheptanoic acid (PFHpA), and perfluorononanoic acid (PFNA) in serum samples collected from pregnant women and the umbilical cord at delivery. Pregnant women (n=101) presenting for second trimester ultrasound were recruited and PFC residue levels were quantified in maternal serum at 24-28 weeks of pregnancy, at delivery, and in umbilical cord blood (UCB; n=105) by liquid chromatography-mass spectrometry. Paired t-test and multiple regression analysis were performed to determine the relationship between the concentrations of each analyte at different sample collection time points. PFOA and PFOS were detectable in all serum samples analyzed including the UCB. PFOS serum levels (mean+/-S.D.) were significantly higher (p<0.001) in second trimester maternal serum (18.1+/-10.9 ng/mL) than maternal serum levels at delivery (16.2+/-10.4 ng/mL), which were higher than the levels found in UCB (7.3+/-5.8 ng/mL; p<0.001). PFHxS was quantifiable in 46/101 (45.5%) maternal and 21/105 (20%) UCB samples with a mean concentration of 4.05+/-12.3 and 5.05+/-12.9 ng/mL, respectively. There was no association between serum PFCs at any time point studied and birth weight. Taken together our data demonstrate that although there is widespread exposure to PFCs during development, these exposures do not affect birth weight.

Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy

Summary:  Purpose: To determine whether long‐term treatment with valproate (VPA) and/or lamotrigine (LTG) in children with epilepsy is associated with altered growth and/or bone metabolism.

Increased Consumption of Dairy Foods and Protein during Diet- and Exercise-Induced Weight Loss Promotes Fat Mass Loss and Lean Mass Gain in Overweight and Obese Premenopausal Women

Weight loss can have substantial health benefits for overweight or obese persons; however, the ratio of fat:lean tissue loss may be more important. We aimed to determine how daily exercise (resistance and/or aerobic) and a hypoenergetic diet varying in protein and calcium content from dairy foods would affect the composition of weight lost in otherwise healthy, premenopausal, overweight, and obese women. Ninety participants were randomized to 3 groups (n = 30/group): high protein, high dairy (HPHD), adequate protein, medium dairy (APMD), and adequate protein, low dairy (APLD) differing in the quantity of total dietary protein and dairy food-source protein consumed: 30 and 15%, 15 and 7.5%, or 15 and <2% of energy, respectively. Body composition was measured by DXA at 0, 8, and 16 wk and MRI (n = 39) to assess visceral adipose tissue (VAT) volume at 0 and 16 wk. All groups lost body weight (P < 0.05) and fat (P < 0.01); however, fat loss during wk 8–16 was greater in the HPHD group than in the APMD and APLD groups (P < 0.05). The HPHD group gained lean tissue with a greater increase during 8–16 wk than the APMD group, which maintained lean mass and the APLD group, which lost lean mass (P < 0.05). The HPHD group also lost more VAT as assessed by MRI (P < 0.05) and trunk fat as assessed by DXA (P < 0.005) than the APLD group. The reduction in VAT in all groups was correlated with intakes of calcium (r = 0.40; P < 0.05) and protein (r = 0.32; P < 0.05). Therefore, diet- and exercise-induced weight loss with higher protein and increased dairy product intakes promotes more favorable body composition changes in women characterized by greater total and visceral fat loss and lean mass gain.

Mineral homeostasis and bone mass at diagnosis in children with acute lymphoblastic leukemia

OBJECTIVE To determine whether the osteopenia and unusual fractures observed in children with acute lymphoblastic leukemia (ALL) were related to the disease rather than to its treatment. DESIGN Prospective analysis of the bone and mineral status in 40 consecutive children with ALL seen in a pediatric tertiary-care referral center. METHODS Biochemical indicators of mineral, endocrine, and vitamin D status were measured before initiation of therapy. Bone mass was determined radiographically and by dual-photon absorptiometry of the lumbar region of the spine (L2-L4). Correlations between clinical observations, leukemia variables, bone mass, and biochemical assessment were determined. RESULTS At the time of diagnosis musculoskeletal pain was present in 36% of patients and was more common in children with CD10-positive leukemia and leukocyte counts less than 20 x 10(9) cells/L. Radiographic evidence of osteopenia and fractures was observed in 13% and 10% of children, respectively. The mean bone mineral content was normal. Bone mass measurement z scores correlated with plasma 1,25-dihydroxyvitamin D3 concentrations (r = 0.43, p < 0.05). Plasma calcium, magnesium, phosphorus, and 25-hydroxyvitamin D3 levels were normal. Low plasma osteocalcin (mean +/- SD, 1.6 +/- 1.6 nmol/L) and 1,25-dihydroxyvitamin D3 (33.4 +/- 26.4 pmol/L) values were observed. Parathyroid hormone levels were low in 14% of children. Hypercalciuria was detected in 64% of children. Urinary deoxypyridinoline was lower (p < 0.01) than in age-matched control subjects. Histomorphometric measurements of iliac bone showed abnormalities in mineralization in the biopsy specimens from three of nine children. CONCLUSION Most children with ALL have alterations in bone metabolism and bone mass when first examined. These data suggest defective mineralization as the mechanism for decreased bone mass and implicate the leukemic process as causative.

Bone and mineral abnormalities in childhood acute lymphoblastic leukemia: influence of disease, drugs and nutrition.

In children with acute lymphoblastic leukemia (ALL), abnormalities in mineral homeostasis and bone mass were first reported by our group in the late 1980s. Prospective longitudinal cohort studies in 40 consecutive patients receiving treatment according to the Dana‐Farber Cancer Institute (DFCI) protocol 87‐001 and 16 children receiving DFCI protocol 91‐001 afforded us the opportunity to explore various etiologies of the observed abnormalities in mineral and bone metabolism, specifically the leukemic disease process and chemotherapeutic drugs such as steroids and aminoglycoside antibiotics. At diagnosis of ALL, >70% of children had abnormally low plasma 1,25‐dihydroxyvitamin D, 73% had low osteocalcin and 64% had hypercalciuria, indicating an effect of the leukemic process on vitamin D metabolism and bone turnover. During remission induction, treatment with high‐dose steroid (prednisone or dexamethasone) resulted in further reduction in plasma osteocalcin and elevated parathyroid hormone levels. During 24 months of chemotherapy‐maintained remission, reduction in bone mineral content (BMC), as measured by Z‐scores, occurred in 64% of children, most severely affecting those >11 years of age. A reduction in BMC during the first 6 months had a positive predictive value of 64% for subsequent fracture. By the end of 2 years of therapy, fractures occurred in 39% of children and radiographic evidence of osteopenia was found in 83% of the entire study group. Investigations of the biochemical basis of the bone abnormalities revealed that by 6 months hypomagnesemia developed in 84% of children (of whom 52% were hypermagnesuric) and plasma 1,25‐dihydroxyvitamin D remained abnormally low in 70%. Altered magnesium status was attributed to renal wastage of magnesium following cyclical prednisone therapy and treatment with aminoglycoside antibiotics such as amikacin for fever accompanying neutropenia. Dietary intake and absorption of magnesium were normal. In 10 children treated for hypomagnesemia with supplemental magnesium for up to 16–20 weeks, plasma magnesium normalized in only 50% of subjects. Int. J. Cancer Supplement 11:35–39, 1998.

Advanced Vertebral Fracture among Newly Diagnosed Children with Acute Lymphoblastic Leukemia: Results of the Canadian STeroid-associated Osteoporosis in the Pediatric Population (STOPP) Research Program

Vertebral compression is a serious complication of childhood acute lymphoblastic leukemia (ALL). The prevalence and pattern of vertebral fractures, as well as their relationship to BMD and other clinical indices, have not been systematically studied. We evaluated spine health in 186 newly diagnosed children (median age, 5.3 yr; 108 boys) with ALL (precursor B cell: N = 167; T cell: N = 19) who were enrolled in a national bone health research program. Patients were assessed within 30 days of diagnosis by lateral thoraco‐lumbar spine radiograph, bone age (also used for metacarpal morphometry), and BMD. Vertebral morphometry was carried out by the Genant semiquantitative method. Twenty‐nine patients (16%) had a total of 75 grade 1 or higher prevalent vertebral compression fractures (53 thoracic, 71%; 22 lumbar). Grade 1 fractures as the worst grade were present in 14 children (48%), 9 patients (31%) had grade 2 fractures, and 6 children (21%) had grade 3 fractures. The distribution of spine fracture was bimodal, with most occurring in the midthoracic and thoraco‐lumbar regions. Children with grade 1 or higher vertebral compression had reduced lumbar spine (LS) areal BMD Z‐scores compared with those without (mean ± SD, −2.1 ± 1.5 versus −1.1 ± 1.2; p < 0.001). LS BMD Z‐score, second metacarpal percent cortical area Z‐score, and back pain were associated with increased odds for fracture. For every 1 SD reduction in LS BMD Z‐score, the odds for fracture increased by 80% (95% CI: 10–193%); the presence of back pain had an OR of 4.7 (95% CI: 1.5–14.5). These results show that vertebral compression is an under‐recognized complication of newly diagnosed ALL. Whether the fractures will resolve through bone growth during or after leukemia chemotherapy remains to be determined.

Skeletal Morbidity in Childhood Acute Lymphoblastic Leukemia

PURPOSE Treatment for acute lymphoblastic leukemia (ALL) in childhood results in a reduction in bone mineral density (BMD). Whether there is a recovery of this lost bone mass in survivors of ALL is not known. We sought to determine if changes in BMD are common long-term sequelae in children with ALL. METHODS Bone mineral densitometry of the lumbar spine and femoral neck was performed on 106 patients. The results were compared with those of age-matched normal controls. The effect of treatment was examined in those with low BMD compared with the remainder of the study group. RESULTS When data were tested with respect to age, sex, and age and sex, no difference was observed in BMD between survivors of childhood ALL and controls. In the subgroup of patients with low BMD, the difference was not related to age, age at diagnosis, or years since diagnosis. Low BMD of the spine was not explained by radiotherapy (RT), methotrexate (MTX) dose, or corticosteroid dose. Low BMD of the femur was not explained by RT. However, those with low femoral BMD were more likely to have received high-dose MTX or higher-dose corticosteroids compared with the remainder of the group. CONCLUSION It appears that survivors of childhood ALL as a whole recover normal BMD. However, those patients who received a total MTX dose of greater than 40000 mg/m(2) or a total corticosteroid dose of greater than 9000 mg/m(2) may not recover normal BMD and therefore should be screened for decreased BMD of the femoral neck.

Improvement in the Accuracy of Dual Energy X-ray Absorptiometry for Whole Body and Regional Analysis of Body Composition: Validation Using Piglets and Methodologic Considerations in Infants

Previously, we conducted dual energy x-ray absorptiometry (DXA) (Hologic QDR-1000/W) scans and carcass analysis of piglets to evaluate the Pediatric Whole Body software (PedWB) (V5.35) for use in infants. A software upgrade designed for infant whole body (InfWB) (V5.56) led to a reassessment of DXA by: 1) reanalysis of the original scans using InfWB software and 2) comparison of InfWB-estimates of bone mineral content (BMC) and lean and fat mass with chemical analysis. Other assessments included 1) methods of regional analysis and 2) artifacts and the Infant Table Pad in the scan field. The mean coefficients of variation for InfWB whole body measures in small piglets(n = 10, weight 1575 ± 73 g) and large piglets (n = 10, weight 5894 ± 208 g) were less than 2.6% except for fat mass which was higher (8.0% versus 6.3% and 6.6% versus 3.5%, respectively) compared with PedWB. In large piglets InfWB produced good estimates of BMC, lean and fat masses. In small piglets, fat mass by InfWB was correlated with chemical analysis, but not by PedWB. There was improvement in the estimation of BMC with InfWB, from 27 ± 2.2 g to 32 ± 2.3 g(carcass ash = 38 ± 3.3 g). Femur BMC analysis by InfWB was precise and was accurate when compared with chemical analysis. Artifacts in the DXA scan field (diapers and blankets) resulted in an increase of the DXA-estimated fat and lean masses. The Infant Table Pad increased the estimate of fat mass in a small piglet by 50%, thus further study is required before it is used routinely. Improvements of the DXA technology have resulted in a more accurate tool, if scanning procedures are carefully implemented.

Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study.

To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk.