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Background: With recent advancements in the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), healthcare specialists may face challenges making treatment and management decisions based on latest evidence for the optimal care of patients with these conditions. This study aimed to identify specific knowledge, skills, and confidence gaps impacting the treatment of CLL and MCL, to inform future educational activities., Methods: Hematologists and hemato-oncologists (HCPs, n = 224) from France (academic settings), Germany, and the United States (academic and community settings) responded to a 15-minute quantitative needs assessment survey that measured perceived knowledge, skills, and confidence levels regarding different aspects of treatment and management of CLL and MCL patients, as well as clinical case questions. Descriptive statistics (cross tabulations) and Chi-square tests were conducted., Results: Four areas of educational need were identified: (1) sub-optimal knowledge of treatment guidelines; (2) sub-optimal knowledge of molecular testing to inform CLL/MCL treatment decisions; (3) sub-optimal skills when making treatment decisions according to patient profile (co-morbidities, molecular testing results); and (4) challenges balancing the risk of toxicities with benefits of treatment. Over one-third of the respondents reported skill gaps when selecting suitable treatment options and prescribing therapies and reported a lack in confidence to initiate and manage treatment. Larger gaps in knowledge of guidelines and skills in patient assessment were identified in MCL, compared to CLL., Conclusions: This study suggests the need for continuing medical education specifically to improve knowledge of treatment guidelines, and to assist clinicians in developing skills and confidence when faced with clinical decision-making scenarios of patients with specific comorbidities and/or molecular test results, for example, through case-based learning activities., (© 2024. The Author(s).)

Objectives: To estimate the proportion of patients with very severe osteoporosis (those covered by the reimbursement criteria of the Italian National Health Service) experiencing new vertebral and non-vertebral fragility fractures in the first 24 months of a new anti-osteoporosis treatment., Methods: Prospective observational study in men and post-menopausal women (aged > 21 years) initiating anti-osteoporosis treatment for very severe osteoporosis. Eligibility was based on teriparatide (TPD) reimbursement criteria in Italy: incident of vertebral or hip fracture during anti-resorptive treatment (minimum 1 year), or at least three prevalent severe vertebral fractures, or two prevalent severe vertebral fractures and a historical proximal hip fracture. Incidence of new clinical vertebral and non-vertebral fractures was documented by original x-rays and/or radiological reports, and a post-hoc analysis compared data from the TPD monotherapy population versus the total treated group., Results: Overall, 767 patients (mean age 72.8 years, 90.7% women) were enrolled in the study, of whom 628, 538, 419 and 424 attended visits at 6, 12, 18 and 24 months, respectively. The most commonly prescribed therapy was TPD (single-agent; 64.5%), then bisphosphonates and other anti-resorptives (33.3%). A combination of different oral treatments was given to 22.5% of the patients. Overall treatment adherence at 24 months was 65.7%. In a post-hoc analysis, the overall incidence of new clinical vertebral and non-vertebral fractures in the total treated population was, respectively, 4.7% and 2.3% in the first 6 months; 1.8% and 1.6% in the 6-12 month period; 2.9% and 1.4% in the 12-18 month period; and 2.2% and 1.0% in the 18-24 month period., Conclusions: In patients with very severe osteoporosis, the risk of new vertebral and non-vertebral fractures declined after the first 6 months and remained low throughout the study.

We investigated possible changes of parameters of calcium metabolism induced by strontium ranelate (SR). Twenty-three patients with postmenopausal osteoporosis (PO) and 14 with primary hyperparathyroidism (PHPT) were studied while taking 2 g/day of SR. Women with PO and 10 healthy age-matched control women were also daily supplemented with 1,000 mg calcium and 800 IU vitamin D. All subjects were studied at baseline and after 7 and 30 days; PO women and controls were also investigated at 180 and 360 days of treatment. Serum ionized calcium (iCa), phosphate (sP), magnesium, creatinine, 25-hydroxycholecalciferol (25[OH]D), 1,25-dihydroxycholecalciferol (1,25[OH](2)D), serum parathyroid hormone (PTH) were measured. In spot urine, we assessed calcium and phosphate over creatinine ratios (uCa/Cr, uP/Cr), calcium excretion (Ca ex) and renal phosphate threshold (TmP/GFR); in 24-h urine, calcium and magnesium over creatinine clearance ratios (CaCl/CrCl and MgCl/CrCl). In PO, SR administration was associated with a significant decrease of PTH and 1,25(OH)(2)D levels but an increase of sP (p < 0.001). SR also significantly increased Ca/Cr, Ca ex, and TmP/GFR in spot urine and CaCl/CrCl in both spot and 24-h urine (p = 0.004 to <0.001). In PHPT, SR significantly decreased iCa and increased sP, slightly modifying PTH, 25(OH)D, and 1,25(OH)(2)D values. Also in PHPT, Ca ex and CaCl/CrCl of spot and 24-h urine, as TmP/GFR, significantly increased (all p < 0.02). SR influenced the main parameters of calcium homeostasis, probably through the calcium-sensing receptor.

Objective: Osteoporosis and hypogonadism are common in men with HIV infection. Ageing Male Symptoms (AMS) scale measures symptoms related to hypogonadism. FRAX provides 10-year probability of major fractures. We investigated the role of AMS scale combined with FRAX without bone mineral density (BMD), in identifying HIV men with bone fragility., Design: Cross-sectional observational study., Methods: Fifty HIV-positive men treated with highly active antiretroviral therapy and 27 controls underwent hormonal evaluation, BMD scan and spine X-ray. The AMS questionnaire was administered., Results: Osteoporosis was found in 24·0% of HIV patients and in 3·7% of controls (P = 0·05). In HIV patients, 9 radiological vertebral fractures were found (none in controls, P = 0·04). Calculated free testosterone suggested hypogonadism in 26% of HIV patients vs 4% of controls (P = 0·04); an abnormal AMS score (≥27) was found in 62% HIV patients compared with 41% controls (P = 0·04). ROC curves showed that FRAX for major fracture had a 23% sensitivity and a 100% specificity in identifying HIV patients with bone fragility (P = 0·002, with the threshold of 7% at which bisphosphonate therapy is cost-effective). Considering a value of AMS ≥27, we obtained an 82·6% sensitivity and a 42·9% specificity (P = 0·04). The combination of AMS and FRAX score achieved a 77·3% sensitivity and a 69% specificity (P = 0·02, cut-off 34)., Conclusion: Combination of FRAX (without BMD) and AMS improved sensitivity of FRAX alone in identifying HIV patients at fracture risk, at the expense of reduced specificity., (© 2012 Blackwell Publishing Ltd.)

The purpose of this study was to evaluate the diagnostic performance of vertebral fracture assessment (VFA) using the Lunar iDXA scanner. Conventional spinal radiographs and images acquired by dual-energy X-ray absorptiometry (DXA) of 350 subjects (269 females, 81 males) were evaluated by two different readers. We visualized 4,476/4,550 (98.4 %) vertebrae from T4 to L4 on VFA images compared to 4,535/4,550 (99.7 %) on radiographs. Among the visualized vertebrae, 205/4,535 (4.5 %) and 190/4,476 (4.2 %) were identified as nonfracture deformities by reading of radiographs and VFA, respectively. Vertebral fractures (VFs) were 231 in 126 patients and 228 in 125 patients by semiquantitative assessment of radiographs (SQ-Rx) and by VFA, respectively. There was excellent agreement between the two techniques and high diagnostic performance of VFA both on a per-vertebra basis (k score = 0.984, 95 % CI 0.972-0.996, sensitivity 98.68 %, specificity 99.91 %, PPV 98.25 %, NPV 99.93 %) and on a per-patient basis (k score = 0.957, 95 % CI 0.925-0.988, sensitivity 96.83 %, specificity 98.66 %, PPV 97.60 %, NPV 98.22 %). In older patients (≥65 years) affected by moderate or severe osteoarthritis, SQ-Rx and VFA identified 96 VFs and 95 versus 90 vertebral deformities, respectively. This study demonstrates that most vertebrae are evaluable using the iDXA scanner, with improved VFA diagnostic performance even in discriminating mild VFs from vertebral deformities. Therefore, VFA may be appropriate as an alternative to conventional radiography in patients at high risk of VF who are undergoing DXA bone densitometry and in the follow-up of osteoporotic patients on treatment.

Introduction: The recent improvement in the resolution of dual-energy X-ray absorptiometry (DXA) images enables most vertebral levels to be seen adequately and thus DXA may be a worthwhile alternative to radiologic morphometry for the identification of vertebral fractures (VF). In this multicenter study, we have derived reference data for vertebral heights and their ratios in Italian women using morphometric X-ray absorptiometry (MXA)., Methods: DXA scans were acquired in 1254 consecutive pre- and postmenopausal women, (mean age 63.7 ± 11.3, range 26-88 yrs), referred to six osteoporosis centers. MXA analysis of these images was performed by the same operator measuring vertebral heights and height ratios from L4 to T4. We calculated measures of central tendency and dispersion of vertebral heights and vertebral ratios using different approaches (mean and standard deviation as well as median and interquartile range of raw data, mean and standard deviation of trimmed data using an iterative algorithm, and mean and standard deviation of not fractured vertebrae)., Results: Independently of the approach that we used, all the measures of central tendency were similar, while significant differences were found when compared with reference ranges in other populations. The vertebral heights of our sample at every vertebral level were significantly smaller than both Rea population and the Lunar reference values, even after normalization. Splitting data according to age groups, there was a decrease in the vertebral heights and ratios between the younger and older women., Conclusions: This study demonstrates that reference data for MXA should be population specific and age matched., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical and etiological factors of osteoporosis. We also tested the FRAX algorithm to compare the assessment of fracture risk in patients with primary or secondary osteoporosis., Methods: A prospective study carried out in a large sample of 123 men and 246 women. All subjects had a biochemical, densitometric, and radiological examination of thoracic and lumbar spine., Results: The prevalence of primary (men 52.9% vs women 50%; p = nonsignificant) and secondary (men 21.1% vs women 17.5%; p = nonsignificant) osteoporosis did not differ between the sexes. In contrast, the prevalence of primary osteoporosis was significantly higher than secondary causes (p < 0.0001) in both men and women. While women came to our attention for prevention of osteoporosis, men sought help because of clinical symptoms or disease-related complications, such as fractures. As evaluated by the FRAX tool, patients with osteopenia do not need treatment, in agreement with Italian guidelines. The estimated risk of major osteoporotic and hip fractures was significantly higher in women with secondary osteoporosis compared to men and also compared to women with primary osteoporosis., Conclusion: The prevalence of secondary osteoporosis in men is similar to that in women and it is less frequent than commonly reported. In patients with secondary osteoporosis, FRAX calculation may provide an estimate of a particularly high fracture risk in patients whose bone fragility is usually attributed to another disease.

Sex steroids play a key role in maintaining skeletal integrity lifelong, through a complex variety of endocrine, but also paracrine and possibly autocrine actions. The current knowledge that androgens may act as pro-hormones for estrogens has seriously challenged many traditional views, so that, at least for their skeletal actions, these can no longer be considered exclusively "male" or "female" hormones., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Several findings indicate that adipose tissue and bone have a complex reciprocal relationship. The two cells lineages share a common progenitor, and adipocyte endocrine activity may influence bone metabolism. Recent evidence from animal models suggests that bone cells may contribute regulating energy metabolism.

Background: Polymorphisms of the sex hormone-binding globulin (SHBG) gene are associated with differences in SHBG levels, influencing the risk for breast cancer and polycystic ovarian syndrome, but no association has been reported for osteoporosis in postmenopausal women., Objective: To determine the effect of G to A substitution in the 5'UTR (rs1799941) and the Asp356Asn (rs6259) polymorphisms of the SHBG gene on bone mineral density (BMD)., Methods: This is a cross-sectional study in a university-based research center from May, 2002 to December, 2007. A total of two hundred and thirteen healthy postmenopausal Caucasian women > or = 1 year from last menstrual period participated to this study. Serum estradiol by ultrasensitive radioimmnunoassay, serum sex hormone-binding globulin by immunoradiometric assay, and urinary NTx by enzyme-linked immunoassay were measured. BMD measurements were performed by dual energy X-ray absorptiometry and genotyping by Pyrosequencing., Results: There were no significant differences in SHBG levels associated with either rs1799941 or rs6259. Using a p value of <0.00625 for significance, we found that subjects with the A allele (GA+AA) for the rs1799941, had a trend for lower free estradiol index (FEI) compared to the GG genotype (p=0.04). They also had significantly lower BMD at the intertrochanter (p=0.003) and trend for lower BMD at the total hip (p=0.02). There was no significant difference in FEI levels between the genotypes for the rs6259 polymorphism, but women with the Asn allele (Asp/Asn+Asn/Asn), had significantly lower BMD in the total femur (p=0.004) and intertrochanter (0.002) compared to those with the Asp/Asp genotype., Conclusions: Our data suggest that polymorphisms of the SHBG gene are associated with significant differences in BMD at the proximal femur sites. Thus, genetic variations in the SHBG gene may influence BMD at the hip in postmenopausal women.

We investigated the frequency of hypercalcemia and/or hypercalciuria following parathyroid hormone (PTH) 1-34 and 1-84 administration in a crossover trial. Ten postmenopausal osteoporotic women previously treated with bisphosphonates were subdivided into two groups of five patients each. A 24-h urine collection to determine baseline calcium (Ca) and creatinine (Cr) the day before administration of PTH was followed by determination of serum ionized Ca (Ca(2+)), Cr, 25(OH)D, and 1,25(OH)(2)D at baseline. Thereafter, 100 mcg of PTH(1-84) or 20 mcg of PTH(1-34) was administered. A 24-h urinary collection and blood samples 2, 4, and 24-h after each PTH administration were again taken. One week after the first PTH administration patients were rechallenged with the second PTH. The PTH peptides did not differ with respect to changes in Ca(2+) at 2, 4, and 24 h postinjection; at the last time point the values were virtually identical to the initial values. There was no difference in urinary Ca on the day following PTH injection compared to baseline, in terms both of Ca/Cr and of Ca excretion. The two PTH peptides did not differ with respect to changes in 1,25(OH)(2)D at 2, 4, and 24 h considering both the absolute values and the percent changes with respect to baseline (24-h 1-84 = 125.6 + or - 58.6 pg/ml, 153% increase; 1-34 = 124.1 + or - 64.7, 130%). Our results indicate no difference in postinjection serum Ca(2+), 1,25(OH)(2)D, or urinary Ca excretion after a single dose of either PTH(1-84) or PTH(1-34) in patients previously treated with bisphosphonates.

Context: An increased risk of fracture in patients with primary hyperparathyroidism (PHPT) compared to the general population has been reported, but available data are controversial., Objective: The aim of the study was to evaluate the rate of vertebral fractures (VFs) by dual-energy x-ray absorptiometry in postmenopausal women with sporadic PHPT and compare the results with a control group., Design and Setting: A case-control study was performed at a referral center., Participants: A total of 150 consecutive patients and 300 healthy women matched for age and menopausal age participated in the study., Results: VFs were detected in 37 of 150 (24.6%) patients and 12 of 300 (4.0%) controls (P < 0.0001). The majority of VFs were mild. Stepwise multiple logistic regression analysis showed that in PHPT patients lumbar spine bone mineral density was the only variable independently associated with the prevalence of VFs (P = 0.003). The rate of fracture was higher in symptomatic (34.1%) than asymptomatic (21.1%) patients, but this difference was not statistically significant (P = 0.15). Among asymptomatic patients, fracture rate was significantly higher in those who met the criteria for parathyroidectomy (28.1%) than in those who did not (11.1%) (P = 0.03). Compared to controls, the fracture rate was significantly higher in patients with symptomatic and asymptomatic PHPT who met the criteria for surgery (P < 0.0001), but not in those who did not meet the criteria (P = 0.06)., Conclusions: VF rate is increased in postmenopausal women with PHPT compared to controls, independently of whether they are classified as symptomatic or asymptomatic. The question of whether the finding of mild morphometric VFs in the latter represents an indication for parathyroid surgery remains to be established.

Following the introduction of corticosteroids as therapeutic agents in the 1950s, their use has been expanded so that today glucocorticoids are widely used. There are few studies in the literature directly aimed at describing the changes of bone markers following glucocorticoid administration. The interpretation of some of these investigations may be hampered by a number of confounding factors, whose influence is not always taken into consideration. In general, the effects of glucocorticoid administration are represented by a reduction in bone formation markers (particularly considering serum osteocalcin levels) and a trend to an increase or no change in bone resorption markers. The inconsistency of this last finding may be related to the time at which the observation is carried out and to the marker employed.