Search PubMed⌕ Search

Biomedical subjects

D Slosman

Publications and source records attributed to D Slosman.

At least 19 recordsLinked to original sources

Longitudinal quality control methodology for the quantitative ultrasound Achilles+ in clinical trial settings.

Appropriate quality assurance (QA) and quality control (QC) procedures have been well developed and validated for dual X-ray absorptiometry (DXA), and are widely applied in multicenter clinical trials to monitor device stability used to check the treatment effects on bone mineral density. This is not yet the case for quantitative ultrasound (QUS) technology, for which no QC approaches have yet been fully tested. The first Achilles (GE-Lunar Corporation, Madison, WI, USA) has been on the market for 10 years (1991). The goal of this study was to develop the QC methodology for the QUS Achilles+ device using its past/current experience (log and maintenance files.) as well as by integrating the progress made over the last years in the ultrasound domain so as to better understand the influence of temperature on ultrasound parameters. Because of the lack of confidence in the external black rubber phantom used in daily QC with the Achilles+, to monitor the device stability, we selected several QC parameters known to be influenced by potential malfunctions as experienced by the maintenance department of GE-Lunar company as well as the physical approach. These are phantom temperature-adjusted speed of sound (PSOS-TC) and broadband ultrasound attenuation (PBUA-TC), water speed of sound error (WSE), water spectrum slope (WSS) and water gain (WG). We used four Achilles+ devices perfectly stable during their entire QC range, to calculate the optimum thresholds (based mostly on 95% confidence interval) for each of these parameters as well as the precision for the in vitro SOS and BUA. An additional not fully stable Achilles device has been used to run a QC procedure example. The precision expressed as the CV was 0.22% and 0.65% for the PSOS-TC and PBUA-TC, respectively. The alarm thresholds used for QC process are +/- 0.6%, +/- 1.9%, +/- 6.8 m/s, +/- 5.3% and +/- 7.3% for the PSOS-TC, PBUA-TC, WSE, WSS and WG, respectively. Applying a logical approach on the impact of each parameter on each other as well as their respective reactivity to malfunctions, we build a QC process flowchart meant to detect real malfunction in the daily QC. We found that in case of real malfunctions, the in vivo SOS should be decreased by 1.33 m/s for each 1 m/s increase in WSE. Unfortunately, in vivo BUA can not be adjusted when real malfunction occurs. Nevertheless, the BUA can be qualified as bad quality data and excluded from the medical interpretation. Using the currently available phantom and parameters, the best possible QC procedures to detect long-term drift in the daily QC of the Achilles+ was developed. To fully validate our approach and gain confidence in the defined limits it is our plan to apply this QC processing to a higher number of QUS devices.

Bone and Bones↗

Gain in bone mineral mass in prepubertal girls 3.5 years after discontinuation of calcium supplementation: a follow-up study.

BACKGROUND: Calcium supplementation during childhood and adolescence increases bone-mass accrual. Whether or not this benefit persists after discontinuation of supplementation is not known. We previously showed a favourable effect of milk-extracted calcium phosphate incorporated in various foods on accumulation of bone mineral mass in 8-year-old girls. We now report the results of a follow-up study undertaken more than 3 years after the end of calcium supplementation. METHODS: Anthropometric and bone variables were measured in 116 of the 144 girls whose data had been studied at the end of the supplementation period. The mean time elapsed between the end of the intervention period and this follow-up measurement was 3.5 years. Areal bone mineral density was measured by dual-energy X-ray absorptiometry at the same six skeletal sites as those studied during the intervention phase. FINDINGS: We were able to remeasure 62 and 54 girls of the calcium-supplemented and placebo groups, respectively. The increase from baseline in the overall mean bone mineral density of the six skeletal sites was still highly significant (calcium-supplemented group 179 mg/cm(2) [SE 8] vs placebo group 151 mg/cm(2) [7], p=0.012). A significant difference in favour of the supplemented group was also seen with respect to mean bone mineral content (p=0.031) and mean bone area (p=0.04). Difference in pubertal maturation did not seem to account for the recorded differences. INTERPRETATION: Our results suggest that this form of milk-extracted calcium phosphate taken during the prepubertal period can modify the trajectory of bone mass growth and cause a long-standing increase in bone mass accrual, which lasts beyond the end of supplementation.

Absorptiometry, Photon↗

Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism.

BACKGROUND: Helical computed tomography (CT) is commonly used to diagnose pulmonary embolism, although its operating characteristics have been insufficiently evaluated. OBJECTIVE: To assess the sensitivity and specificity of helical CT in suspected pulmonary embolism. DESIGN: Observational study. SETTING: Emergency department of a teaching and community hospital. PATIENTS: 299 patients with clinically suspected pulmonary embolism and a plasma D -dimer level greater than 500 microgram/L. INTERVENTION: Pulmonary embolism was established by using a validated algorithm that included clinical assessment, lower-limb compression ultrasonography, lung scanning, and pulmonary angiography. MEASUREMENTS: Sensitivity, specificity, and likelihood ratios of helical CT and interobserver agreement. Helical CT scans were withheld from clinicians and were read 3 months after acquisition by radiologists blinded to all clinical data. RESULTS: 118 patients (39%) had pulmonary embolism. In 12 patients (4%), 2 of whom had pulmonary embolism, results of helical CT were inconclusive. For patients with conclusive results, sensitivity of helical CT was 70% (95% CI, 62% to 78%) and specificity was 91% (CI, 86% to 95%). Interobserver agreement was high (kappa = 0.823 to 0.902). The false-negative rate was lower for helical CT used after initial negative results on ultrasonography than for helical CT alone (21% vs. 30%). Use of helical CT after normal results on initial ultrasonography and nondiagnostic results on lung scanning had a false-negative rate of only 5% and a false-positive rate of only 7%. CONCLUSION: Helical CT should not be used alone for suspected pulmonary embolism but could replace angiography in combined strategies that include ultrasonography and lung scanning.

Adult↗

Allogeneic bone marrow transplantation is associated with a preferential femoral neck bone loss.

Osteoporosis is a major complication of organ transplantation. Little is known about the risk of developing osteoporosis in bone marrow transplant (BMT) recipients. We studied early and late changes in bone mineral density (BMD), as well as biochemical markers of bone remodeling, in patients at the time of allogeneic BMT (alloBMT) and up to 13 years thereafter. In a cross-sectional study, 102 patients (40 women, 62 men, mean age +/- SEM, 38.9 +/- 1.6 years) were segregated into a first group (A, n = 48) and evaluated before or during the first weeks (mean +/- SD 0.3 +/- 0.1 month, range -0.5 to 3 months) following alloBMT, and a second group (B, n = 54) studied 60.1 +/- 5.6 months (range 6-156 months) following alloBMT. Lumbar spine (LS) BMD was similar in groups A and B and was within normal limits. In contrast, femoral neck (FN) Z- and T-scores were significantly decreased in group B compared with group A (-0.68 +/- 0.14 vs -0.03 +/- 0.14 SD and -0.84 +/- 0.14 vs -0.22 +/- 0.14 SD, respectively; p < or = 0.002). Osteopenia (T-score between -1 and -2.5 SD) was present in 35% of group A and 43% of group B patients (NS). Osteoporosis (T-score < -2.5 SD) was detected in 7% of group B patients, but in none of those in group A (p = 0.05). In a longitudinal study, 56 subjects were evaluated at the time of alloBMT, and 33 and 23 were studied 6 or 12 months later, respectively (13 women, 20 men, 37.5 +/- 1.6 years). All were treated with supplements of calcium and vitamin D. Amenorrheic women received hormone replacement therapy (HRT). Three-monthly pamidronate infusions were given to 15 men and 10 non-amenorrheic women who were osteopenic/osteoporotic or had elevated baseline bone turnover markers. Mean baseline LS and FN Z- and T-scores were within normal range. Six months after BMT, FN BMD decreased by 4.2 +/- 0.7% (p < 0.001), and whole body BMD and bone mineral content by 1.5 +/- 0.4% and 3.1 +/- 0.6%, respectively (p < or = 0.0001). Twelve months after the graft, there was no further significant bone loss and only FN BMD decrease remained significantly different compared with baseline (-5.6 +/- 1.1%, p < or = 0.0001). These results indicate that the risk of decreased BMD is higher for the femoral neck than the lumbar spine and whole body levels in patients with allogeneic bone marrow transplantation, and that bone loss occurs mainly during the first 6 months after the graft.

Adolescent↗

Functional neuroanatomical correlates of hysterical sensorimotor loss.

Hysterical conversion disorders refer to functional neurological deficits such as paralysis, anaesthesia or blindness not caused by organic damage but associated with emotional "psychogenic" disturbances. Symptoms are not intentionally feigned by the patients whose handicap often outweighs possible short-term gains. Neural concomitants of their altered experience of sensation and volition are still not known. We assessed brain functional activation in seven patients with unilateral hysterical sensorimotor loss during passive vibratory stimulation of both hands, when their deficit was present and 2-4 months later when they had recovered. Single photon emission computerized tomography using (99m)Tc-ECD revealed a consistent decrease of regional cerebral blood flow in the thalamus and basal ganglia contralateral to the deficit. Independent parametric mapping and principal component statistical analyses converged to show that such subcortical asymmetries were present in each subject. Importantly, contralateral basal ganglia and thalamic hypoactivation resolved after recovery. Furthermore, lower activation in contralateral caudate during hysterical conversion symptoms predicted poor recovery at follow-up. These results suggest that hysterical conversion deficits may entail a functional disorder in striatothalamocortical circuits controlling sensorimotor function and voluntary motor behaviour. Basal ganglia, especially the caudate nucleus, might be particularly well situated to modulate motor processes based on emotional and situational cues from the limbic system. Remarkably, the same subcortical premotor circuits are also involved in unilateral motor neglect after organic neurological damage, where voluntary limb use may fail despite a lack of true paralysis and intact primary sensorimotor pathways. These findings provide novel constraints for a modern psychobiological theory of hysteria.

Adolescent↗

Astrocytes as a predominant cellular site of (99m)Tc-HMPAO retention.

Technetium-99m-d,l-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) retention in the brain monitored by single photon emission computed tomography (SPECT) is currently used as a marker of cerebral blood flow. The purported mechanism by which (99m)Tc-HMPAO accumulates in the brain is through its intracellular conversion from a lipophilic form to more hydrophilic derivatives within the brain parenchyma. The issue of the contribution of different cell types on (99m)Tc-HMPAO retention was investigated in vitro by studying the accumulation of (99m)Tc-HMPAO in primary cultures of mouse cortical astrocytes and neurons. Results show that (99m)Tc-HMPAO retention predominates in astrocytes over neurons by a factor of approximately 2.5 (0.26 +/- 0.05 vs. 0.095 +/- 0.042 fmol/mg protein after 120 minutes, respectively). Diethyl maleate (60 micromol/L), ethacrynic acid (1 mmol/L) and buthionine sulfoximine (1 mmol/L), 3 agents which significantly reduced glutathione levels also decreased (99m)Tc-HMPAO retention in both astrocytes (29%, 3%, and 46% of control, respectively) and neurons (69%, 11% and 63% of control). Decrease did not always correlate with glutathione levels, however, which suggests that other factors could be involved. The possibility that cell energy status determines (99m)Tc-HMPAO retention was also assessed. Agents that activate (glutamate, azide) or inhibit (cytochalasin B) glucose utilization in astrocytes, as measured by the (3)H-2-deoxyglucose method, were without effect on (99m)Tc-HMPAO retention. In conclusion, the data presented indicate that astrocytes may constitute a prominent site of (99m)Tc-HMPAO retention and most likely contribute significantly to the SPECT signal. In addition, the data also suggest that specific alterations in glial cell metabolism could explain flow-independent changes in (99m)Tc-HMPAO retention in the brain as observed by SPECT in some pathologies.

Animals↗

Oligo-amenorrheic long-distance runners may lose more bone in spine than in femur.

PURPOSE: Strenuous training can be associated with amenorrhea leading to amenorrhea-related accelerated bone loss. Insufficient calorie energy, calcium, and/or protein intakes can also be frequently encountered in women with intense training, possibly contributing to bone loss. Long-distance runners with or without regular menses (age range 19-37 yr) were prospectively studied. METHODS: Changes in areal bone mineral density (BMD) were measured at 1-yr interval. RESULTS: Among 10 eumenorrheic, 11 oligo-amenorrheic, and 9 oral contraceptive users, there was no difference in energy, calcium, or protein intakes. Baseline BMD values were significantly lower in the oligo-amenorrheic group than in the two others at the level of lumbar spine (anteroposterior view: 0.941+/-0.039 in oligo-amenorrheic vs 1.077+/-0.029 or 1.051 +/-0.017 g x cm(-2), P < 0.005, in the eumenorrheic and contraceptive user groups, respectively) but not in weight-bearing bone such as proximal and midshaft femur. Over a 1-yr interval, during which the three groups did not differ in terms of running distances and dietary intakes, oligo-amenorrheic women displayed a significant decrease in lumbar spine BMD in lateral view (-0.049+/-0.012 in oligo-amenorrheic vs -0.001+/-0.013 and 0.014+/-0.012 g x cm(-2), p < 0.005, in the eumenorrheic and contraceptive user groups, respectively). We did not detect any significant change in femoral neck, trochanter, or midshaft BMD. CONCLUSIONS: Oligo-amenorrhea in long-distance runners, with adequate dietary intakes, was associated with a decrease in BMD affecting more the lumbar spine than the proximal and midshaft femur during a 1-yr follow-up.

Adult↗

Randomised controlled trial of three day versus 10 day intravenous antibiotics in acute pyelonephritis: effect on renal scarring.

BACKGROUND: Acute pyelonephritis often leaves children with permanent renal scarring. AIMS: To compare the prevalence of scarring following initial treatment with antibiotics administered intravenously for 10 or three days. METHODS: In a prospective two centre trial, 220 patients aged 3 months to 16 years with positive urine culture and acute renal lesions on initial DMSA scintigraphy, were randomly assigned to receive intravenous ceftriaxone (50 mg/kg once daily) for 10 or three days, followed by oral cefixime (4 mg/kg twice daily) to complete a 15 day course. After three months, scintigraphy was repeated in order to diagnose renal scars. RESULTS: Renal scarring developed in 33% of the 110 children in the 10 day intravenous group and 36% of the 110 children in the three day group. Children older than 1 year had more renal scarring than infants (42% (54/129) and 24% (22/91), respectively). After adjustment for age, sex, duration of fever before treatment, degree of inflammation, presence of vesicoureteric reflux, and the patients' recruitment centres, there was no significant difference between the two treatments on renal scarring. During follow up, 15 children had recurrence of urinary infection with no significant difference between the two treatment groups. CONCLUSION: In children with acute pyelonephritis, initial intravenous treatment for 10 days, compared with three days, does not significantly reduce the development of renal scarring.

Acute Disease↗

Prediction of pulmonary embolism extent by clinical findings, D-dimer level and deep vein thrombosis shown by ultrasound.

Pulmonary embolism (PE) may encompass a wide spectrum of severity. To determine whether clinical findings, D-dimer (DD) concentration, and deep vein thrombosis (DVT) shown by lower-limb venous compression ultrasonography (US) might predict the scintigraphic extent of PE, we studied 104 hemodynamically stable consecutive outpatients with acute PE diagnosed by a high-probability ventilation-perfusion lung scan. Scintigraphic extent of PE was classified into three categories: perfusion defects corresponding to <30%, 30-50%, or >50% of the total lung area. Median respiratory and heart rates were found to be significantly related to the extent of PE. Higher median alveolar-arterial oxygen difference values were observed as the proportion of lung perfusion defects increased (>50% vs. <30%, 6.3 vs. 3.6 kPa, P <.0001). Median plasma DD concentration was 7950 microg/L in patients with >50% perfusion defects compared to 2731 microg/L in those with <30% defects (P = .0001). DD levels above 4000 microg/L were associated to more extensive perfusion defects (>50% vs. <30% defects, OR 30; 95% CI 5.8-155). Finally, a proximal DVT was more likely among patients with larger perfusion defects (>50% vs. <30% defects, OR 4.5; 95% CI 1.5-13.6). In conclusion, clinical signs such as tachypnea and tachycardia, alveolar-arterial oxygen difference, plasma DD concentration, and presence of DVT on US are predictors of a larger PE, as assessed by the extent of perfusion defects on high probability lung scans.

Adult↗

Using clinical evaluation and lung scan to rule out suspected pulmonary embolism: Is it a valid option in patients with normal results of lower-limb venous compression ultrasonography?

BACKGROUND: In patients with a low clinical probability of pulmonary embolism (PE) and a nondiagnostic lung scan, the prevalence of PE is theoretically very low. We assessed the safety and usefulness of this association for ruling out PE. METHODS: We analyzed data from 2 consecutive cohort management studies performed in 2 university hospitals (Geneva University Hospital, Geneva, Switzerland, and Hospital Saint-Luc, Montreal, Quebec), which enrolled 1034 consecutive patients who came to the emergency department with clinically suspected PE. All patients were submitted to a sequential diagnostic protocol of lung scan, D-dimer testing, lower-limb venous compression ultrasonography (US), and pulmonary angiography in case of inconclusive results of noninvasive workup. RESULTS: The prevalence of PE was 27.6%. Empirical assessment was accurate for identifying patients with a low likelihood of PE (8.2% prevalence of PE in the low clinical probability category). One hundred eighty patients had a low clinical probability of PE and a nondiagnostic lung scan. Among these patients, US showed deep vein thrombosis in 5. Hence, PE could be ruled out by a low clinical probability, a nondiagnostic lung scan, and a normal US in 175 patients (21.5%). The 3-month thromboembolic risk in these patients was low (1.7%; 95% confidence interval, 0.4%-4.9%). CONCLUSIONS: Anticoagulant treatment could be safely withheld in patients with a low clinical probability of PE and a nondiagnostic lung scan, provided that the US is normal. This combination of findings avoided pulmonary angiography in 21.5% of patients with suspected PE in this series.

Adult↗

Similarity and robustness of PET and SPECT binding parameters for benzodiazepine receptors.

The single photon emission computed tomography (SPECT) radiotracer [123I]iomazenil is used to assess benzodiazepine receptor binding parameters. These measurements are relative indices of benzodiazepine receptor concentration (B'max). To evaluate the ability of such indices in accurately accessing the B'max the authors compared them with absolute values of B'max, measured using positron emission tomography (PET). The authors performed SPECT, PET, and magnetic resonance imaging (MRI) studies on a group composed of seven subjects. For SPECT studies, the authors administered a single injection of [123I]iomazenil and estimated the total and specific distribution volumes (DV(T SPECT), DV(S SPECT)) and the binding potential (BP) using unconstrained (BP(SPECT)) and constrained (BP(C SPECT)) compartmental models. For PET studies, the authors used a multiinjection approach with [11C]flumazenil and unlabeled flumazenil to estimate absolute values of receptor concentration, B'max, and some other binding parameters. The authors studied the correlation of different binding parameters with B'max. To study the robustness of the binding parameter measurements at the pixel level, the authors applied a wavelet-based filter to improve signal-to-noise ratio of time-concentration curves, and the calculated kinetic parameters were used to build up parametric images. For PET data, the B'max and the DV(PET) were highly correlated (r = 0.988). This confirms that it is possible to use the DV(PET) to access benzodiazepine receptor density. For SPECT data, the correlation between DV(SPECT) estimated using a two- and three-compartment model was also high (r = 0.999). The DV(T SPECT) and BP(C SPECT) parameters estimated with a constrained three-compartment model or the DV(T''SPECT) parameter estimated with a two-compartment model were also highly correlated to the B'max parameter estimated with PET. Finally, the robustness of the binding parameters allowed the authors to build pixel-by-pixel parametric images using SPECT data.

Adult↗

[Value of positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) in early detection of residual tumor in oro-pharyngeal-laryngeal carcinoma].

OBJECTIVE: To evaluate and compare the performances of FDG-PET imaging, MRI and clinical examination in the detection of residual tumour 3 months after treatment of patients with head and neck squamous cell carcinoma. PATIENTS: A consecutive sample of 50 patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, or a cervical lymph node metastasis from an unknown primary site excluding T1 lip and T1 vocal cord tumours. METHODS: Treatment outcome was assessed after 3 months by clinical examination, MRI, and FDG-PET scan. Sensitivity, specificity and accuracy were calculated relative to proven biopsy of residual tumour or a clinical follow-up of 4 months. RESULTS: Residual cancer was confirmed in 8 patients (16%), while the clinical follow-up was unsuspicious in the remaining 42 patients. PET-FDG had a sensitivity of 100% as compared to MRI (88%) and clinical examination (63%). Specificity was higher for clinical examination (90%), intermediate for MRI (83%) and lowest for PET-FDG (74%). CONCLUSIONS: This study finds very high sensitivity for PET-FDG in the detection of residual tumour. However, its lower specificity, lack of anatomical resolution, and high cost, require further studies to determine its role in routine screening.

Biopsy↗

Encephalopathy with epileptic spasms resolved with corticoids in a 69 year-old patient.

A 69 year-old man with a history of recent temporal lobe seizures, presented with progressive coma and frequent epileptic spasms. Ictal EEG, PET and SPECT alterations were strikingly similar to those described in infantile spasms. Conventional antiepileptic drugs were ineffective but the introduction of corticoids induced a dramatic improvement with disappearance of the spasms. The etiology remains unknown. Epileptic spasms may occur in the elderly. If conventional antiepileptic drugs are ineffective, corticoids should be tried immediately.

Aged↗

Non-invasive diagnosis of venous thromboembolism in outpatients.

BACKGROUND: We designed a simple and integrated diagnostic algorithm for acute venous thromboembolism based on clinical probability assessment of deep-vein thrombosis (DVT) or pulmonary embolism (PE), plasma D-dimer measurement, lower-limb venous compression ultrasonography, and lung scan to reduce the need for phlebography and pulmonary angiography. METHODS: 918 consecutive patients presenting at the emergency ward of the Geneva University Hospital, Geneva, Switzerland, and Hôpital Saint-Luc, Montreal, Canada, with clinically suspected venous thromboembolism were entered into a sequential diagnostic protocol. Patients in whom venous thromboembolism was deemed absent were not given anticoagulants and were followed up for 3 months. FINDINGS: A normal D-dimer concentration (<500 microg/L by a rapid ELISA) ruled out venous thromboembolism in 286 (31%) members of the study cohort, whereas DVT by ultrasonography established the diagnosis in 157 (17%). Lung scan was diagnostic in 80 (9%) of the remaining patients. Venous thromboembolism was also deemed absent in patients with low to intermediate clinical probability of DVT and a normal venous ultrasonography (236 [26%] patients), and in patients with a low clinical probability of PE and a non-diagnostic result on lung scan (107 [12%] patients). Pulmonary angiography and phlebography were done in only 50 (5%) and 2 (<1%) of the patients, respectively. Hence, a non-invasive diagnosis was possible in 866 (94%) members of the entire cohort. The 3-month thromboembolic risk in patients not given anticoagulants, based on the results of the diagnostic protocol, was 1.8% (95% CI 0.9-3.1). INTERPRETATION: A diagnostic strategy combining clinical assessment, D-dimer, ultrasonography, and lung scan gave a non-invasive diagnosis in the vast majority of outpatients with suspected venous thromboembolism, and appeared to be safe.

Acute Disease↗

Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry.

The presence of Sr in bone influences bone mineral density (BMD) and content (BMC) measurements by dual-energy X-ray absorptiometry (DXA). This interaction is of interest, since strontium ranelate (S12911) demonstrated positive effects on bone metabolism in various animal models of osteoporosis, and is currently being evaluated for treatment of postmenopausal osteoporosis. The present in vitro study aimed to determine adjustment factors for DXA measurements of BMC and BMD at different Sr concentrations in order to estimate the corresponding values that would have been measured without Sr. A series of mixtures of Ca and Sr hydroxyapatites were prepared, with biologically relevant Sr/Ca ratios ranging from 0 to 3.5 mol/mol%, and a constant total concentration of divalent cations (145 mmol). The mixtures were conditioned in plastic dishes 4.5 cm in diameter, to obtain an areal density close to the human vertebral mineral density of 0.7-1.1 g/cm(2). DXA measurements of the mixtures were made with a wide range of different instruments and various acquisition modes. A direct linear relationship (r(2) > 0.99) was found between strontium content and overestimation of BMD and BMC. There were no significant differences in adjustment factors for BMC or BMD between the different machines or acquisition modes, and the presence of Sr in the water bath used to mimic soft tissues did not affect the accuracy and precision of the method. This demonstrates that reliable DXA determinations of BMD may be carried out in the presence of Sr, and may be interpreted in terms of calcium hydroxyapatite equivalent if the bone Sr content of the measured bone is known. The same adjustment factor (10% overestimation for 1 mol/mol% Sr) can be used for all presently available types of instrument and acquisition modes.

Absorptiometry, Photon↗

Bone mineral mass and calcium and phosphate metabolism in young men: relationships with vitamin D receptor allelic polymorphisms.

The genetic bases of peak bone mass determinants are still poorly understood, particularly in males. We investigated the relationship between vitamin D receptor (VDR) 3'- and 5'-gene polymorphisms (as determined by the restriction enzymes BsmI and FokI) and bone mineral mass, and calcium and inorganic phosphate (Pi) metabolism in an homogeneous cohort of young healthy men. In 104 healthy subjects, aged 24.3 +/- 3.1 yr (mean +/- SD; range, 20.7-38.7), standardized bone mineral density (BMD; z-scores) at the levels of lumbar spine and femoral trochanter, i.e. bone mineral content adjusted for age, body size, and bone area, significantly differed between VDR 3'-end alleles (BsmI), whereas crude areal BMD or bone mineral content did not. Among BsmI homozygotes BB, BMD (z-scores) were significantly lower only in subjects also carrying the f allele at the VDR-5' polymorphic site (FokI). Serum PTH levels were significantly higher in the BB genotype at baseline and remained so under either a low or a high calcium-phosphorus diet. Moreover, on the low calcium-phosphorus diet, BB subjects had significantly decreased tubular Pi reabsorptive capacity and plasma Pi levels. Our results underline the importance of identifying multiple single base mutation polymorphisms within candidate genes of bone mineral mass and suggest a role for environmental/dietary factor interactions with VDR gene polymorphisms in peak bone mineral mass in men.

Adult↗

Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Elderly persons who have osteoporotic hip fracture are often undernourished, particularly with respect to protein. Protein malnutrition may contribute to the occurrence and outcome of hip fracture. OBJECTIVE: To investigate whether oral protein supplements benefit bone metabolism in patients with recent hip fracture. DESIGN: 6-month, randomized, double-blind, placebo-controlled trial with a 6-month post-treatment follow-up. SETTING: University orthopedic ward. PATIENTS: 82 patients (mean age, 80.7 +/- 7.4 years) with recent osteoporotic hip fracture. Patients received calcium supplementation, 550 mg/d, and one dose of vitamin D, 200,000 IU (at baseline). INTERVENTION: Protein supplementation, 20 g/d, or isocaloric placebo (among controls). MEASUREMENTS: Bone mineral density, biochemical markers of bone remodeling, calciotropic hormone levels, biochemically evaluated nutritional and immunologic status, and muscle strength were measured every 6 months. RESULTS: Compared with controls, patients who received protein supplements had significantly greater increases in serum levels of insulin-like growth factor-I (85.6% +/- 14.8% and 34.1% +/- 7.2% at 6 months; difference, 51.5 percentage points [95% CI, 18.6 to 84.4 percentage points]; P = 0.003) and an attenuation of the decrease in proximal femur bone mineral density (-2.29% +/- 0.75% and -4.71% +/- 0.77% at 12 months; difference, 2.42 percentage points [CI, 0.26 to 4.59 percentage points]; P = 0.029). Seven and 13 new vertebral deformities were found among patients who received protein supplements and controls, respectively (P > 0.2). Median stay in rehabilitation wards was shorter for patients who received protein supplements than for controls (33 days [CI, 29 to 56 days] and 54 days [CI, 44 to 62 days]; difference, 21 days [CI, 4 to 25 days]; P = 0.018). CONCLUSION: Protein repletion after hip fracture was associated with increased serum levels of insulin-like growth factor-I, attenuation of proximal femur bone loss, and shorter stay in rehabilitation hospitals.

Activities of Daily Living↗

Familial resemblance for bone mineral mass is expressed before puberty.

Genetic factors are known to explain a major proportion of peak bone mineral mass variance. Whether the influence of these genetic factors is expressed before the pubertal bone mineral mass accrual and whether there is tracking of bone mineral mass during pubertal growth, however, are not clearly established. We prospectively investigated correlations for bone mineral content (BMC), density, and bone size between prepubertal daughters and their premenopausal mothers. Height, weight, lumbar spine (LS), femoral neck (FN) and mid-femoral diaphysis BMC, bone area (BA), areal bone mineral density (aBMD), and volumetric bone mineral apparent density (BMAD) were evaluated in 138 mothers (mean age +/- SD, 40.0 +/- 4.0 yr) and their daughters (8.1 +/- 0.7 yr), who were then remeasured at yearly intervals for 2 yr. Eight-year-old prepubertal daughters had reached 78% and 44% of their mothers' height and weight, respectively. At the various skeletal sites, they had reached 33-43% of their mothers' BMC, 47-69% of their BA, 59-78% of their aBMD, and 75-105% of their BMAD. All body size and bone traits (age-adjusted Z-scores) were significantly correlated between prepubertal daughters and their mothers (r: 0.22-0.36, P < 0.01), except midfemoral diaphysis BMAD. Heritability estimates (1/2 h2), after adjustment for body size and dietary calcium intake, showed that 18-37% of bone traits were directly determined by maternal descent. During the next 2 yr, growth was accompanied by a marked increase of BMC, aBMD, and BA, whereas BMAD changed very little. In contrast, during this period, there were only minor changes in body size or bone trait Z-scores (i.e. < 0.5 Z-scores), which were thus highly correlated between consecutive measurements (r: 0.75-0.92, P < 0.0001). Accordingly, mother-daughter correlations remained unchanged over that period. Although more than 60% of peak bone mineral mass is gained during puberty (mostly at the expense of an increase in bone size while volumetric bone density slightly changes), familial resemblance for most bone traits is already present between daughters and their mothers before puberty. In the girls, moreover, yearly measurements were highly correlated, suggesting tracking of bone traits during pubertal growth. These results indicate that genetic susceptibility to osteoporosis may already be detectable in early childhood.

Adult↗