scholarly journals Bone density and metabolism in subjects with microdeletion of chromosome 22q11 (del22q11)

2010 ◽  
Vol 163 (2) ◽  
pp. 329-337 ◽  
Author(s):  
Stefano Stagi ◽  
Elisabetta Lapi ◽  
Eleonora Gambineri ◽  
Cristina Manoni ◽  
Maurizio Genuardi ◽  
...  

IntroductionAlthough 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.DesignThis study aimed to evaluate bone mass and metabolism in a cohort of patients, both children and adults, with 22q11DS.MethodsIn 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.ResultsPatients 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.ConclusionsSubjects 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.

2010 ◽  
Vol 37 (9) ◽  
pp. 1935-1943 ◽  
Author(s):  
STEFANO STAGI ◽  
LAURA MASI ◽  
SERENA CAPANNINI ◽  
ROLANDO CIMAZ ◽  
GIULIA TONINI ◽  
...  

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.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2940-2940
Author(s):  
Sofia Jonsson ◽  
Yuan Wei ◽  
Bob Olsson ◽  
Claes Ohlsson ◽  
Mattias Lorentzon ◽  
...  

Abstract Background: Imatinib mesylate (Gleevec™) is the drug of choice for most patients with chronic phase CML. It was recently suggested that hypophosphatemia develops in imatinib treated patients as a consequence of suppression of bone turnover and renal phosphate wasting. Aim: To study the mineral metabolism, and areal and volumetric bone mineral density in chronic phase CML patients treated with imatinib. Material and methods: Seventeen imatinib treated CML patients (11 males/6 females; mean age 60±11 (SD) years) and 17 healthy volunteers (11 males/6 females; mean age 59±11 (SD) years) were included. All CML patients were treated in first chronic phase, targeting an imatinib dose of 400 mg q.d. At time of study, all patients were in complete cytogenetic remission and the mean imatinib treatment duration was 50±19 (SD) months. Serum levels of total and ionized calcium, phosphate, magnesium, parathyroid hormone (PTH), and markers of bone formation (osteocalcin and bone specific alkaline phosphatase) and bone resorption (carboxyterminal cross-linked telopeptide of type I collagen) were analyzed. Twenty-four hours urine collections, for determination of calcium and phosphate excretion, were also obtained from all patients and controls. Areal and volumetric bone mineral density (aBMD and vBMD) were evaluated by dual energy x-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT), respectively. Results: Imatinib treated patients had significantly lower serum levels of ionized calcium, phosphate, magnesium, osteocalcin and bone specific alkaline phosphatase. Serum PTH was higher in the patients compared the controls (p=0.06). The patients also excreted less calcium in the urine. aBMD were increased in hip and lumbar spine compared to controls. The results of the DXA measurements. T-score is the difference of BMD from young adult (20–40 years; same sex) mean value normalised to the population SD. Z-score is the difference of BMD from age-matched (same sex) mean value normalised to the population SD. vBMD was increased in cortical but not trabecular bone of tibia and radius. The results of pQCT-measurements. vBMD and cross sectional area were measured at *4% and **25% bone length in the proximal direction. Conclusion: Our data show that imatinib increases cortical bone mineral density and clearly rules out the previous concern of “imatinib induced osteomalacia”. It can be speculated that tyrosine kinase inhibitors could be novel antiosteolytic agents in skeletal disorders such as osteoporosis, myelomatosis and bone marrow metastatic diseases. Indeed, previous animal studies have shown that imatinib decreases osteoclastogenesis and osteoclast activity. DXA CML (n=17) Controls (n=17) P-value Hip bone (total) aBMD (g/cm2) 1.08±0.2 0.95±0.1 0.025 T-score 0.07±1.42 −0.82±0.83 Z-score 0.46±1.37 −0.26±0.85 Lumbar spine aBMD (g/cm2) 1.27±0.22 1.12±0.15 0.029 T-score 0.38±1.77 −0.82±1.23 Z-score 0.57±1.72 −0.36±1.29 pQCT CML (=17) Controls (n=17) P-value Radius Trabecular vBMD* (mg/cm3) 190.9±34.2 193.9±28.8 ns Cortical vBMD** (mg/cm3) 1211.3±23.8 1181.1±38.7 0.01 Cortical area** (mm2) 95.1±16.3 88.6±18.7 ns Tibia Trabecular vBMD* (mg/cm3) 240.2±47.3 226.2±23.9 ns Cortical vBMD* (mg/cm3) 1185.6±23.5 1159.4±36.2 0.017 Cortical area** (mm2) 262.6±50.7 261.3±44.4 ns


2013 ◽  
Vol 110 (6) ◽  
pp. 1061-1067 ◽  
Author(s):  
M. S. Fewtrell ◽  
K. Kennedy ◽  
Peter R. Murgatroyd ◽  
J. E. Williams ◽  
S. Chomtho ◽  
...  

Few studies have investigated the effects of infant nutrition on later bone health in term infants, although low sn-2 palmitate in infant formulas has been shown to result in the formation of stool fatty acid soaps, reduced Ca absorption and lower bone mass in the short term. To investigate the effect of (1) breast-feeding (BF) and (2) the type of infant formula (standard fat blend v. high-sn-2 fat blend) on bone mass at age 10 years, anthropometry and bone mass (from dual-energy X-ray absorptiometry (GE Lunar Prodigy); lumbar spine (LS) and total body less head; adjusted for size (bone mineral apparent density standard deviation score (SDS) and regression)) were measured in 10-year-old subjects born at term and either breast-fed (n 34) or randomised to a standard control formula (n 27) or a high-sn-2 palmitate formula (n 30) for the first 12 weeks of life. At follow-up, previously BF children were older but lighter (by 0·5 SDS, P= 0·03) than formula-fed children with a lower LS bone mineral density SDS (by 0·44, P= 0·03), but size-adjusted bone mass did not differ. There were no significant differences in bone mass between the formula-fed groups. These findings suggest that there is no significant effect of BF or high-sn-2 infant formula on size-adjusted bone mass in mid-childhood, and that the effects of infant nutrition on bone mass previously reported may be confined to the short term. A larger study would be required to exclude smaller effects.


Author(s):  
Hsin-Hua Chou ◽  
Sao-Lun Lu ◽  
Sen-Te Wang ◽  
Ting-Hsuan Huang ◽  
Sam Li-Sheng Chen

The association between osteoporosis and periodontal disease (PD) has been revealed by previous studies, but there have been few studies on the association in younger adults. We enrolled a total of 7298 adults aged 40 to 44 who underwent PD screening between 2003 and 2008. Data on quantitative ultrasound for the measurement of bone mineral density (BMD) were collected for the diagnostic criteria of osteopenia and osteoporosis. The Community Periodontal Index (CPI) was measured for defining PD. A multiple logistic regression model was used to assess the effect of low bone mass on the risk of PD. Of 7298 enrollees, 31% had periodontal pockets >3 mm, 36.2% had osteopenia, and 2.1% had osteoporosis. The 39.8% of PD prevalence was high in adults with osteoporosis, followed by 33.3% in osteopenia. A negative association was found between BMD and CPI value (p < 0.0001). Low bone mass was associated with the risk of PD (adjusted OR: 1.13; 95% CI:1.02–1.26) after adjusting the confounding factors, including age, gender, education level, overweight, smoking status, past history of osteoporosis, and diabetes mellitus. An association between BMD and PD among young adults was found. An intervention program for the prevention of PD and osteoporosis could be considered starting in young adults.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2075
Author(s):  
Anne Daly ◽  
Wolfgang Högler ◽  
Nicola Crabtree ◽  
Nick Shaw ◽  
Sharon Evans ◽  
...  

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein glycomacropeptide substitutes (CGMP-AA) as their main protein source. Methodology: A total of 48 subjects completed the study, 19 subjects in the L-AA group (median age 11.1, range 5–6 years) and 29 subjects in the CGMP-AA group (median age 8.3, range 5–16years). The CGMP-AA was further divided into two groups, CGMP100 (median age 9.2, range 5–16years) (n = 13), children taking CGMP-AA only and CGMP50 (median age 7.3, range 5–15years) (n = 16), children taking a combination of CGMP-AA and L-AA. Dual X-ray absorptiometry (DXA) was measured at enrolment and 36 months, peripheral quantitative computer tomography (pQCT) at 36 months only, and serum blood and urine bone turnover markers (BTM) and blood bone biochemistry at enrolment, 6, 12, and 36 months. Results: No statistically significant differences were found between the three groups for DXA outcome parameters, i.e., BMDa (L2–L4 BMDa g/cm2), bone mineral apparent density (L2–L4 BMAD g/cm3) and total body less head BMDa (TBLH g/cm2). All blood biochemistry markers were within the reference ranges, and BTM showed active bone turnover with a trend for BTM to decrease with increasing age. Conclusions: Bone density was clinically normal, although the median z scores were below the population mean. BTM showed active bone turnover and blood biochemistry was within the reference ranges. There appeared to be no advantage to bone density, mass, or geometry from taking a macropeptide-based protein substitute as compared with L-AAs.


Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1895
Author(s):  
Francesca Marini ◽  
Francesca Giusti ◽  
Federica Cioppi ◽  
Davide Maraghelli ◽  
Tiziana Cavalli ◽  
...  

Primary hyperparathyroidism (PHPT) is the most common endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Persistent levels of increased parathyroid hormone (PTH) result in a higher incidence of osteopenia and osteoporosis compared to the general population. Surgical removal of hyper-functioning parathyroid tissue is the therapy of choice. This retrospective study evaluated the effect of parathyroidectomy (PTX) on bone metabolism and bone mass in two series of patients with MEN1 PHPT and sporadic PHPT (sPHPT) by comparing bone metabolism-related biochemical markers and bone mineral density (BMD) before and after surgery. Our data confirmed, in a higher number of cases than in previously published studies, the efficacy of PTX, not only to rapidly restore normal levels of PTH and calcium, but also to normalize biochemical parameters of bone resorption and bone formation, and to improve spine and femur bone mass, in both MEN1 PHPT and sPHPT. Evaluation of single-patient BMD changes after surgery indicates an individual variable bone mass improvement in a great majority of MEN1 PHPT patients. In MEN1 patients, PTX is strongly suggested in the presence of increased PTH and hypercalcemia to prevent/reduce the early-onset bone mass loss and grant, in young patients, the achievement of the bone mass peak; routine monitoring of bone metabolism and bone mass should start from adolescence. Therapy with anti-fracture drugs is indicated in MEN1 patients with BMD lower than the age-matched normal values.


2011 ◽  
Vol 212 (2) ◽  
pp. 179-186 ◽  
Author(s):  
Rana Samadfam ◽  
Malaika Awori ◽  
Agnes Bénardeau ◽  
Frieder Bauss ◽  
Elena Sebokova ◽  
...  

Peroxisome proliferator-activated receptor (PPAR) γ agonists, such as pioglitazone (Pio), improve glycemia and lipid profile but are associated with bone loss and fracture risk. Data regarding bone effects of PPARα agonists (including fenofibrate (Feno)) are limited, although animal studies suggest that Feno may increase bone mass. This study investigated the effects of a 13-week oral combination treatment with Pio (10 mg/kg per day)+Feno (25 mg/kg per day) on body composition and bone mass parameters compared with Pio or Feno alone in adult ovariectomized (OVX) rats, with a 4-week bone depletion period, followed by a 6-week treatment-free period. Treatment of OVX rats with Pio+Feno resulted in ∼50% lower fat mass gain compared with Pio treatment alone. Combination treatment with Pio+Feno partially prevented Pio-induced loss of bone mineral content (∼45%) and bone mineral density (BMD; ∼60%) at the lumbar spine. Similar effects of treatments were observed at the femur, most notably at sites rich in trabecular bone. At the proximal tibial metaphysis, concomitant treatment with Pio+Feno prevented Pio exacerbation of ovariectomy-induced loss of trabecular bone, resulting in BMD values in the Pio+Feno group comparable to OVX controls. Discontinuation of Pio or Feno treatment of OVX rats was associated with partial reversal of effects on bone loss or bone mass gain, respectively, while values in the Pio+Feno group remained comparable to OVX controls. These data suggest that concurrent/dual agonism of PPARγ and PPARα may reduce the negative effects of PPARγ agonism on bone mass.


2012 ◽  
Vol 25 (3) ◽  
pp. 331-340 ◽  
Author(s):  
Susan Ziglar ◽  
Tracy S. Hunter

Maximizing bone mass in youth is touted as the best strategy to offset the natural losses of aging and the menopausal transition. Not achieving maximum peak bone mineral density (BMD) is an independent risk factor for osteoporosis and thus a public health concern. Adolescence is a critical time of bone mineralization mediated by endogenous estradiol. Research has shown that the highest velocity of bone mass accrual occurs 1 year before menarche and after the first 3 years. Low-peak attainment of BMD in young women is associated with contributing factors such as diets low in calcium, eating disorders, lack of exercise, smoking, and low estrogen states. Oral contraceptives (OCs) suppress endogenous estradiol production by suppressing the hypothalamic–pituitary–ovarian axis. Thus, OCs, by replacing endogenous estradiol with ethinyl estradiol (EE), establish and maintain new hormone levels. The early initiation and the use of very low dose of EE raises the possibility that bone mass accrual at a critical time of bone mineralization in young women or adolescents may be jeopardized. This review examines the studies of BMD in adolescents and young women that use combination hormonal contraception. Some studies had inherent limitations, such as small trial, poor control of confounders, failure to exclude women with prior use of hormonal contraceptives, or prior pregnancy from control groups. The vast majority of reviewed studies showed OCs containing 20 to 30 µg of EE interfere with acquisition of peak BMD. Limited numbers of studies examine the effects of OCs containing 35 µg on adolescents and young adults. Additionally, studies are needed evaluating the progestin component of OCs as their differing androgenic properties may affect bone mineralization as well.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
Radwa Helmy Shalaby ◽  
Elham Mohamed Kassem ◽  
Nagat Mohamed El-Gazzar ◽  
Sahar Ahmed Fathy Hammoudah ◽  
Amal Mohamed El-Barbary

Abstract Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic arthropathy of childhood and is associated with low bone mass, and may hasten the onset of osteoporosis later in life1. Bone loss occurs because of an imbalance between osteoclasts-activating factors like receptor activator of nuclear factor-κB ligand (RANKL) and its inhibitor osteoprotegerin (OPG) 2. Dual energy X-ray absorptiometry (DXA) is the preferred method for measuring bone mineral density (BMD) in children and to identify and follow individuals at risk for fracture 3. The objective is the Evaluation of serum levels of osteoprotegerin and RANKL and their correlation with BMD in JIA patients. Methods Forty JIA patients (according to the revised classification criteria of ILAR) and 40 healthy children individually matched for age, sex and race were included in this study. Children excluded from the study were those with primary and secondary causes of osteoporosis (such as chronic illness). All patients were assessed clinically by: age, sex, body mass index, type of JIA, disease duration and disease activity (by Juvenile Arthritis Disease Activity Score; JADAS 10). The functional disability was assessed by the Childhood Health Assessment Questionnaire (CHAQ). Blood samples were collected from JIA patients and healthy controls to determine serum levels of OPG and RANKL by ELISA. DXA scans were done using GE Healthcare Lunar DPX, Madison, Wisconsin. Bone mineral density of the L1-L4 lumbar spine and total body less head (TBLH) was evaluated in g/cm2 and expressed as Z score for age, sex according to the reference data given for this equipment. Results The study included 40 patients (25 females) with a mean age of 11.14 years and median disease duration of 2.5 years. As regard JIA type, 45% of patients were oligoarticular, 32.5% were polyarticular, and 22.5% were systemic JIA. Median JADAS 10 was 13.95. Patients (especially polyarticular JIA) had significantly higher serum RANKL levels and lower serum OPG and OPG/RANKL ratio when compared with controls (with p-value &lt;0.001, 0.032 and &lt;0.001 respectively). A diagnosis of low BMD (BMD Z-score ≤ -2) was given in 25% of patients (15% polyarticular and 10% systemic) by DXA of lumbar spine, and 20% (10% polyarticular and 10% systemic) by DXA of TBLH. On the other hand, no patient was given a diagnosis of osteoporosis (BMD Z-score ≤ -2 and a significant fracture history). Low BMD at lumbar spine and TBLH was negatively correlated with serum RANKL while positively correlated with OPG/RANKL ratio. Moreover, low BMD at lumbar spine was positively correlated with serum OPG level Conclusion High RANKL and low OPG levels appear to be associated with low bone mass in JIA patients. Patients with JIA (especially polyarticular and systemic subtype) are at increased risk of low bone mineral mass. Disclosure of Interests None declared


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