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Objective: To evaluate bone mineral status and metabolism in a cohort of patients with Williams-Beuren syndrome (WBS)., Patients: Thirty-one children (15 females, 16 males; mean age 9.6±2.74 years) and 10 young adults (6 females, 4 males; mean age 21.4±5.11 years) with WBS were cross-sectionally evaluated and compared with two age-, sex-, and body-size-matched paediatric (155 subjects, 75 females and 80 males; mean age 9.7±2.93 years) and adult (50 subjects, 30 females and 20 males; mean age 22.3±5.42 years) healthy controls., Measurements: We evaluated ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels, and urinary deoxypyridinoline concentrations. We also calculated the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) z-scores., Results: WBS patients showed a significantly reduced AD-SoS z-score (p <0.001) and BTT z-score (p <0.001) compared with the controls. This finding persisted when we divided the sample into paediatric and adult patients. WBS patients also had significantly higher ionised (p <0.001) and total calcium (p <0.001) levels as well as higher PTH levels (p <0.001) compared with the controls. Furthermore, WBS children and adolescents had significantly lower serum osteocalcin levels (p <0.001) and urinary deoxypyridinoline concentrations (p <0.001) than controls., Conclusions: WBS subjects exhibit a significant reduction in bone mineral status and impaired bone metabolism. These findings point to the need for close monitoring of WBS patients.

More and more data seem to indicate the presence of an increasing number of syndromes and genetic diseases characterized by impaired bone mass and quality. Meanwhile, the improvement of etiopathogenetic knowledge and the employment of more adequate treatments have generated a significant increase in survival related to these syndromes and diseases. It is thus important to identify and treat bone impairment in these patients in order to assure a better quality of life. This review provides an updated overview of bone pathophysiology and characteristics in patients with Down, Turner, Klinefelter, Marfan, Williams, Prader-Willi, Noonan, and 22q11 deletions syndrome. In addition, some options for the treatment of the bone status impairment in these patients will be briefly discussed.

Background: Few prospective data have been published on the comparison of bone density and quality in homogeneous groups of patients with juvenile systemic lupus erythematosus (JSLE) and juvenile idiopathic arthritis (JIA)., Objective and Hypothesis: The objective of this study is to perform a longitudinal evaluation of the prevalence and the characteristics of bone mass and quality and to evaluate the differences on the bone parameters, using DXA, pQCT and QUS., Population And/or Methods: Forty-three JSLE patients (35 females, 8 males, median age 18.8, range 14.0-34.1 years) have been studied with DXA, pQCT and QUS scans and compared with 138 JIA patients (112 females, 26 males, median age 18.9, range 13.4-33.2 years), and 79 controls (59 females, 20 males; median age 19.3, range 13.5-36.5 years). Of these, 39 patients (32 females and 7 males, median age 20.3, range 16.6-36.8 years) with JSLE were followed longitudinally and compared with 131 patients (108 females, 23 males median age 20.7, range 15.8-37.1 years) with JIA and 63 controls (48 females, 15 males; median age 21.9, range 15.5-38.3 years)., Results: JSLE patients have a higher bone cortical density (CrtBMD) than controls and JIA patients (p < 0.005). However, JSLE and JIA patients have a significantly reduced bone trabecular density (TrbBMD) compared to controls (p < 0.0001), with no differences between JSLE and JIA. In addition, JIA patients show a significantly reduced muscle area (MuscleCSA) compared to JSLE and controls (p < 0.001). Conversely, fat area (FatCSA) is significantly increased both in JIA and JSLE patients when compared to controls (p < 0.001), with no differences between the JSLE and JIA groups. Analogous results are observed in the polar resistance to stress (SSIp). On longitudinal evaluation, contrary to CrtBMD, the difference between BMAD SDS, TrbBMD, MuscleCSA and FatCSA remains unchanged; in JSLE patients, SSIp is stable in comparison to JIA and controls without any difference between the two groups., Conclusions: The evaluation of bone density and structure parameters in JSLE patients highlights significant differences compared with JIA patients and controls. These data might indicate a different pathogenesis of bone damage in the two entities, and suggest a different diagnostic and therapeutic approach to improve the peak bone mass., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Introduction: There are few prospective data on bone mass and quality in patients with juvenile onset systemic lupus erythematosus (JSLE). There are also few studies analyzing bone mass and quality determinants by using at the same time dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and quantitative ultrasound (QUS)., Objective: The objective of this paper is to evaluate cross-sectionally and longitudinally bone mass and quality determinants in adolescents and young adults with JSLE, and to identify the main predictors of reduced bone mineral density (BMD) and bone quality using these techniques., Methods: Fifty-six patients with JSLE (mean age 18.5 ± 5.7 years) entered the study. In all subjects DXA scan at the lumbar spine, radius pQCT and phalangeal QUS were performed the same day. Of these, 46 patients (mean age 23.1 ± 6.2 years) were revaluated with a second DXA, pQCT and QUS. The data obtained were compared with 72 and 80 age- and sex- matched healthy controls., Results: At the first evaluation, JSLE patients had a reduced spine BMAD SDS (p < 0.001), and significantly lower levels of TrabBMD (p < 0.0001), SSIp (p < 0.05), AD-SoS and QUS z-score (p < 0.005) but not reduced muscle CSA and CBA values. CortBMD and FatCSA were significantly increased (p < 0.0001). These data were confirmed at longitudinal evaluation regarding spine BMAD SDS (p < 0.001), TrabBMD (p < 0.0001), FatCSA (p < 0.005), AD-SoS (p < 0.001), and QUS z-score (p < 0.005) but not muscle CSA (p ≤ 0.05) and CBA (p < 0.0001). SSIp and CortBMD longitudinal evaluation showed that JSLE patients did not present significant differences in comparison to controls., Conclusions: Patients with JSLE have a low bone mass without catch-up growth over time, causing a reduction of peak bone mass with high risk of osteoporosis in early adulthood. To reduce the risk, close monitoring of BMD, better control of disease activity, physical activity and dietary intake of calcium and vitamin D are advocated to ameliorate the loss of bone mass. In patients with proved osteoporosis therapeutic approaches including bisphosphonates should be considered.

Objective: To assess the prevalence of reduced spine bone mineral apparent density (BMAD), and to identify the main predictors of reduced spine BMAD in a cross-sectional and longitudinal evaluation of the same large cohort of patients with juvenile idiopathic arthritis (JIA). There are few prospective data on bone mass evaluation in a large number of patients with JIA, and with enthesitis-related arthritis onset., Methods: Two hundred nineteen patients with JIA (median age 8.7 yrs, range 6.1-13.1 yrs; 104 oligoarticular JIA, 61 polyarticular, 20 systemic, and 34 enthesitis-related arthritis onset) were retrospectively evaluated. A dual-energy x-ray absorptiometry (DEXA) scan at the lumbar spine was performed in all subjects. Of these, 89 consecutive patients were followed up randomly and longitudinally with a second and a third DEXA evaluation. The data obtained were compared with 80 age-matched and sex-matched healthy subjects., Results: At the first DEXA, patients with JIA showed a reduced spine BMAD standard deviation score (SDS) in comparison to controls (p < 0.001). These results were confirmed when the subjects were divided into JIA subtypes (p < 0.005) with the exception of enthesitis-related arthritis onset. Spine BMAD SDS significantly correlated with JIA onset type (p < 0.01), age at JIA onset (p < 0.005), and flares (p = 0.008). The longitudinal evaluation showed that spine BMAD SDS did not significantly improve at the followup in comparison to controls, in all subsets with JIA except for systemic onset (p < 0.05). Spine BMAD correlated with sex (p < 0.01), systemic corticosteroid exposure (p < 0.01), the number of intraarticular corticosteroid injections (p < 0.01), the interval from last steroid injection (p < 0.05), erythrocyte sedimentation rate (p < 0.005), and C-reactive protein levels (p < 0.005)., Conclusion: Patients with JIA have a low bone mass and, after a first increase due to therapy, do not reach a healthy condition over time despite our current more effective drugs. These patients have a high risk of osteoporosis in early adulthood. To reduce the risk and improve the bone mass, close monitoring of bone mineral density, better control of disease activity, physical activity, and intake of calcium and vitamin D are recommended. In patients with osteoporosis, therapeutic approaches including bisphosphonates should be considered.

Introduction: Although hypoparathyroidism with hypocalcaemia is one of the most frequent clinical features of monoallelic microdeletion of chromosome 22q11 (22q11DS), bone mass and metabolism have not yet been assessed in these patients., Design: This study aimed to evaluate bone mass and metabolism in a cohort of patients, both children and adults, with 22q11DS., Methods: In twenty-eight patients with 22q11DS (median age 12.5, range 6.1-42.8 years), serum levels of ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin and bone-specific alkaline phosphatase (BSAP), and urinary deoxypyridinoline concentrations were evaluated. In these patients, bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DXA) examination, and volumetric BMD (bone mineral apparent density (BMAD)) was calculated. The data obtained from paediatric and adult patients were compared with two age-, sex- and body size-matched healthy subject control groups., Results: Patients with 22q11DS showed a reduced BMAD Z-score compared with controls (P<0.001). These patients also had significantly lower ionised (P<0.001) and total calcium (P<0.05) levels as well as lower PTH levels (P<0.05), compared with the controls. In particular, children and young patients with 22q11DS had significantly lower serum osteocalcin levels (P<0.001), BSAP levels (P<0.001) and urinary deoxypyridinoline concentrations (P<0.001) than controls. These results were not confirmed in adults. Finally, patients with hypoparathyroidism and/or hypocalcaemia at the time of the study showed significantly lower ionised (P<0.001) and total calcium levels (P<0.001), PTH levels (P<0.05), BSAP levels (P<0.001), osteocalcin levels (P<0.001) and urinary deoxypyridinoline concentrations (P<0.001), compared with patients without hypoparathyroidism and/or hypocalcaemia. Nonetheless, the BMAD Z-score did not show substantial differences between these two groups., Conclusions: Subjects with 22q11DS have a significant reduction in bone mass that appears to be more severe in adults who have already attained peak bone mass than in children who are still growing. Therefore, we suggest a close monitoring of bone mass and metabolism in 22q11DS patients.

Objective: To evaluate bone mineral status over 1 yr of etanercept treatment in juvenile idiopathic arthritis (JIA)., Methods: Twenty children (13 female, 7 male) aged 5.2-11.4 yr, with active polyarticular JIA were prospectively enrolled to receive etanercept (0.4 mg/kg, twice weekly). Responders were defined according to the American College of Rheumatology Pediatric 50 definition of improvement. Broadband ultrasound attenuation (BUA) by bone was determined at the left calcaneus to assess bone status at baseline and at 1-yr follow-up., Results: After 12 months of treatment, 15 (75%) patients were considered as responders. At baseline, responders and non-responders did not differ with regard to age, disease duration, core-set variables or BUA and Z-score values (patient's value--age specific normal value/normal group's s.d.). At 6-month and 1-yr follow-up in the whole group, BUA and Z-score values were not significantly different compared with baseline. At 1-yr follow-up, but not at 6 months, all 15 responders, differently from non-responders, showed a significant increase in both BUA and Z-score values: BUA at 1 yr 55.2 +/- 3.3 vs baseline 43.5 +/- 3.2 dB/MHz, P<0.001; Z score at 1 yr -0.3 +/- 0.2 vs baseline 1.5 +/- 0.4, P<0.002., Conclusion: For the first time in childhood rheumatic disease this pilot prospective study, although in a small group, shows evidence that 1 yr of etanercept therapy by controlling the underlying disease activity induces a sustained benefit on JIA bone loss. Prospective studies in larger patient samples are needed to confirm these data.

Objective: To compare bone density with polymorphisms in the calcitonin receptor (CTR) and vitamin D receptor (VDR) genes in 50 patients with juvenile idiopathic arthritis and 80 matched controls., Methods: Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry at the lumbar spine. Genomic DNA was isolated from EDTA blood samples by standard procedures. Polymerase chain reaction was performed using genomic DNA and 100 pmol of each oligonucleotide primer for VDR and CTR genes. Products from genomic PCR were digested by Alu I enzyme for CTR polymorphism and Fok I enzyme for VDR polymorphism., Results: In the total population, higher prevalence of CC genotype (41.5%) for the CTR gene and FF genotype (59.8%) for the VDR gene was found, in agreement with data for Caucasian populations. No significant differences in distribution of CTR and VDR genotypes were observed between patients and controls. However, patients with TT genotype had lumbar BMD (L-BMD) that was lower in comparison to those with CC genotype (p = 0.04). For VDR gene polymorphism, we observed that patients with ff genotype had lower L-BMD in comparison with FF genotype (p = 0.02). Patients with heterozygosity for the 2 genotypes showed intermediate L-BMD. The differences in L-BMD among these groups did not seem to be related to corticosteroid therapy., Conclusion: Our data suggest that patients with particular VDR and CTR genotypes may be at higher risk to lose bone mass.