Bone mineral density is within normal range in most adult phenylketonuria patients.
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ABSTRACT:
SUBMITTER: Lubout CMA
PROVIDER: S-EPMC7078943 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Bone mineral density is within normal range in most adult phenylketonuria patients.
Lubout Charlotte M A CMA Arrieta Blanco Francisco F Bartosiewicz Katarzyna K Feillet François F Gizewska Maria M Hollak Carla C van der Lee Johanna H JH Maillot François F Stepien Karolina M KM Wagenmakers Margreet A E M MAEM Welsink-Karssies Mendy M MM van Spronsen Francjan J FJ Bosch Annet M AM
Journal of inherited metabolic disease 20200206 2
Low bone mineral density (BMD) as a risk factor for fractures has been a long-standing concern in phenylketonuria (PKU). It is hypothesised that the disease itself or the dietary treatment might lead to a low BMD. Previous studies show conflicting results of BMD in PKU due to differences in age, techniques to assess BMD and criteria used. To assess the prevalence of low BMD and define possible risk factors in a large number of adult, early treated PKU (ETPKU) patients. European centres were invi ...[more]
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Project description:BACKGROUND:Growing evidence indicates that homocysteine is a noteworthy marker for general health status. However, research regarding plasma total homocysteine (tHcy) levels and bone mineral density (BMD) is sparse and controversial. Hence, we aimed to investigate the association between plasma tHcy level within normal range and lumbar BMD in adults. METHODS:In this cross-sectional study, using the National Health and Nutrition Examination Survey database, data on 10748 adults aged between 30 and 85?years were analyzed. The weighted multiple logistic regression analyses were conducted to evaluate the association between plasma tHcy level and lumbar BMD. The fitted smoothing curves were performed to explore potential non-linear relationships. When non-linearity was detected, we further calculated the inflection point using a recursive algorithm and constructed a weighted two-piecewise linear regression model. RESULTS:After adjusting for all the covariates, the association between plasma tHcy and lumbar BMD was different in various age groups (adults aged 30-49?years: ? = -0.0004, 95% CI -0.0025, 0.0018; adults aged 50-69?years: ? = 0.0001, 95% CI -0.0025, 0.0026; adults aged 70-85?years: ? = 0.0050, 95% CI 0.0008, 0.0092). In the subgroup analysis stratified by gender, this association also differed based on gender. There was a negative trend in females (aged 30-49?years: ? = -0.0022, 95% CI -0.0054, 0.0011; aged 50-69?years: ? = -0.0028, 95% CI -0.0062, 0.0007), and a positive trend in males (aged 30-49?years: ? = 0.0018, 95% CI -0.0012, 0.0048; aged 50-69?years: ? = 0.0027, 95% CI -0.0009, 0.0063) in both 30-49?years group and 50-69?years group. In the 70-85?years group, this association was significantly positive in males (? = 0.0136, 95% CI 0.0068, 0.0204), but was not significantly different in females (? = 0.0007, 95% CI -0.0046, 0.0060). CONCLUSION:The correlation between plasma tHcy level within the normal range and lumbar BMD differs by age and gender.
| S-EPMC7559759 | biostudies-literature
Project description:INTRODUCTION:Our objective was to systematically review and analyze published data on bone mineral density (BMD) and fracture rates in patients with phenylketonuria (PKU), and relationships between BMD and phenylalanine levels. METHODOLOGY:We searched PubMed, CINAHL, and Cochrane databases from January 1966 to November 2013 for studies of spine BMD or fracture in PKU and control subjects. We excluded studies assessing skeletal health by ultrasound or peripheral quantitative computer tomography. Both authors reviewed abstracts for inclusion, and read full text papers to extract data. RESULTS:Sixteen studies met eligibility criteria. Meta-analysis of three studies found that spine BMD was 0.100 g/cm(2) lower (95% CI, -0.110, -0.090 g/cm(2)) in 67 subjects with PKU, compared to 161 controls. Among six studies, 20% (53 of 263) of PKU subjects experienced clinical fractures. In the single study with controls, the fracture rate was 2.6 fold higher (95% CI, 1.1-6.1) after age 8 in PKU subjects, compared to healthy sibling controls. When considering a total of 12 studies in 412 subjects, nine or 75% of studies representing 71% of studied subjects reported no association between phenylalanine levels and BMD. Spine BMD is lower in PKU than control subjects, but only one study controlled for smaller body size. Existing studies suggest a clinical fracture rate of 20% among PKU subjects, but fracture rates in controls are lacking. Finally, existing data shows no consistent relationship between phenylalanine levels and BMD. Future studies are needed to clarify the etiology and health consequences of low BMD in PKU.
| S-EPMC4208974 | biostudies-literature
Project description:In adult hypophosphatasia (HPP) patients, elevated lumbar spine dual X-ray absorptiometry (DXA) values are associated with markers of disease severity and disease-specific fracture risk while femoral bone mineral density (BMD), being largely unaffected by the disease severity, may still be useful to monitor other causes of increased fracture risk due to low BMD.IntroductionHypophosphatasia (HPP) is a rare inherited metabolic disorder due to deficient activity of the tissue-nonspecific alkaline phosphatase (TNAP). Clinical manifestation in adult HPP patients is manifold including an increased risk for fractures, but data regarding clinical significance of DXA measurement and associations with fracture risk and disease severity is scarce.MethodsRetrospective single-center analysis of DXA scans in patients with confirmed HPP (documented mutation, clinical symptoms, low alkaline phosphatase activity). Further data evaluation included disease-related fractures, laboratory results (alkaline phosphatase, pyridoxalphosphate, phosphoethanolamine), and medical history.ResultsAnalysis included 110 patients (84 female, mean age of 46.2 years) of whom 37.3% (n = 41) were harboring two mutations. Average T-Score level at the lumbar spine was - 0.1 (SD 1.9), and mean total hip T-Score was - 1.07 (SD 0.15). Both lower ALP activity and higher substrate levels (pyridoxalphosphate and phosphoethanolamine) were significantly correlated with increased lumbar spine T-Score levels (p < 0.001) while BMD at the hip was not affected by indicators of disease severity. Increased lumbar spine BMD was significantly associated with an increased risk for HPP-related fractures, prevalent in 22 (20%) patients (p < 0.001) with 21 of them having biallelic mutations.ConclusionBMD in adult HPP patients is not systematically reduced. Conversely, increased lumbar spine BMD appears to be associated with severely compromised mineralization and increased risk for HPP-related fractures while BMD at the hip appears unaffected by indicators of disease severity, suggesting suitability of this anatomic location for assessing and discerning disorders with increased fracture risk owing to reduced BMD like osteoporosis.Trial registration numberGerman register for clinical studies (DRKS00014022) DATE OF REGISTRATION: 02/10/2018 - retrospectively registered.
| S-EPMC7838076 | biostudies-literature
Project description:The incidence of osteoporotic fractures increases as our population ages. Until now, the exact biochemical processes that occur during the healing of metaphyseal fractures remain unclear. Diagnostic instruments that allow a dynamic insight into the fracture healing process are as yet unavailable. In the present matched pair analysis, we study the time course of the osteoanabolic markers bone specific alkaline phosphatase (BAP) and transforming growth factor ?1 (TGF?1), as well as the osteocatabolic markers crosslinked C-telopeptide of type-I-collagen (?-CTX) and serum band 5 tartrate-resistant acid phosphatase (TRAP5b), during the healing of fractures that have a low level of bone mineral density (BMD) compared with fractures that have a normal BMD. Between March 2007 and February 2009, 30 patients aged older than 50 years who suffered a metaphyseal fracture were included in our study. BMDs were verified by dual energy Xray absorptiometry (DXEA) scans. The levels of BTMs were examined over an 8-week period. Osteoanabolic BAP levels in those with low levels of BMD were significantly different from the BAP levels in those with normal BMD. BAP levels in the former group increased constantly, whereas the latter group showed an initial strong decrease in BAP followed by slowly rising values. Osteocatabolic ?-CTX increased in the bone of the normal BMD group constantly, whereas these levels decreased significantly in the bone of the group with low BMD from the first week. TRAP5b was significantly reduced in the low level BMD group. With this work, we conduct first insights into the molecular biology of the fracture healing process in patients with low levels of BMD that explains the mechanism of its fracture healing. The results may be one reason for the reduced healing qualities in bones with low BMD.
| S-EPMC4006874 | biostudies-literature
Project description:Background:Low bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU). Objective:To determine if there are differences in BMD and body composition between male and female participants with PKU. Methods:From our randomized, crossover trial [1] of participants with early-treated PKU who consumed a low-phenylalanine (Phe) diet combined with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF), a subset of 15 participants (6 males, 9 females, aged 15-50 y, 8 classical and 7 variant PKU) completed one dual energy X-ray absorptiometry (DXA) scan and 3-day food records after each dietary treatment. Participants reported lifelong compliance with AA-MF. In a crossover design, 8 participants (4 males, 4 females, aged 16-35 y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1-3 weeks each. Results:Male participants had significantly lower mean total body BMD Z-scores (means ± SE, males = - 0.9 ± 0.4; females, 0.2 ± 0.3; p = 0.01) and tended to have lower mean L1-4 spine and total femur BMD Z-scores compared to female participants. Only 50% percent of male participants had total body BMD Z-scores above - 1.0 compared to 100% of females (p = 0.06). Total femur Z-scores were negatively correlated with intake of AA-MF (r = - 0.58; p = 0.048). Males tended to consume more grams of protein equivalents per day from AA-MF (means ± SE, males: 67 ± 6 g, females: 52 ± 4 g; p = 0.057). Males and females demonstrated similar urinary excretion of renal net acid, magnesium and sulfate; males showed a trend for higher urinary calcium excretion compared to females (means ± SE, males: 339 ± 75 mg/d, females: 228 ± 69 mg/d; p = 0.13). Females had a greater percentage of total fat mass compared to males (means ± SE, males: 24.5 ± 4.8%, females: 36.5 ± 2.5%; p = 0.047). Mean appendicular lean mass index was similar between males and females. Male participants had low-normal lean mass based on the appendicular lean mass index. Conclusions:Males with PKU have lower BMD compared with females with PKU that may be related to higher intake of AA-MF and greater calcium excretion. The trial was registered at www.clinicaltrials.gov as NCT01428258.
| S-EPMC6047464 | biostudies-literature
Project description:Previous studies have identified 63 single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD) in adults. These SNPs are thought to reflect variants that influence bone maintenance and/or loss in adults. It is unclear whether they affect the rate of bone acquisition during adolescence. Bone measurements and genetic data were available on 6397 individuals from the Avon Longitudinal Study of Parents and Children at up to five follow-up clinics. Linear mixed effects models with smoothing splines were used for longitudinal modelling of BMD and its components bone mineral content (BMC) and bone area (BA), from 9 to 17 years. Genotype data from the 63 adult BMD associated SNPs were investigated individually and as a genetic risk score in the longitudinal model. Each additional BMD lowering allele of the genetic risk score was associated with lower BMD at age 13 [per allele effect size, 0.002 g/cm(2) (SE = 0.0001, P = 1.24 × 10(-38))] and decreased BMD acquisition from 9 to 17 years (P = 9.17 × 10(-7)). This association was driven by changes in BMC rather than BA. The genetic risk score explained ∼2% of the variation in BMD at 9 and 17 years, a third of that explained in adults (6%). Genetic variants that putatively affect bone maintenance and/or loss in adults appear to have a small influence on the rate of bone acquisition through adolescence.
| S-EPMC4476449 | biostudies-literature
Project description:BackgroundPatients with inherited bone marrow failure syndromes (IBMFS) may have several risk factors for low bone mineral density (BMD). We aimed to evaluate the prevalence of low BMD in IBMFS and determine the associated risk factors.MethodsPatients with IBMFS with at least one dual-energy X-ray absorptiometry (DXA) scan were evaluated. Diagnosis of each IBMFS, Fanconi anemia (FA), dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome was confirmed by syndrome-specific tests. Data were gathered on age, height, and clinical history. DXA scans were completed at the lumbar spine, femoral neck, and forearm. BMD was adjusted for height (HAZ) in children (age ≤20 years). Low BMD was defined as a BMD Z-score and HAZ ≤-2 in adults and children, respectively, in addition to patients currently on bisphosphonate therapy.ResultsNine of thirty-five adults (26%) and eleven of forty children (27%) had low BMD. Adults with FA had significantly lower BMD Z-scores than those with other diagnoses; however, HAZ did not vary significantly in children by diagnosis. Risk factors included hypogonadism, iron overload, and glucocorticoid use.ConclusionsAdults and children with IBMFS have high prevalence of low BMD. Prompt recognition of risk factors and management are essential to optimize bone health.
| S-EPMC5570650 | biostudies-literature
Project description:BackgroundExposure to heavy metals from environmental and industrial sources remains a concern of serious public health risk. This study was conducted to analysis the relationship between heavy metal concentrations and bone density.MethodsThis study used data from a nation-based sample of Koreans (n=2,429) from 2008 to 2011 Korea National Health and Nutrition Examination Survey. We were obtained heavy metals (lead, mercury and cadmium), socioeconomic and demographic factors and bone mineral density (BMD) measured by T-score.ResultsMenopausal women, current smoker or the frequent alcohol drinking, low educational level and low family income were greater in the osteopenia or osteoporosis groups than normal group, and were associated with an increased blood heavy metal concentration levels. The highest quartile group in blood lead had a 1.47 times (95% confidence interval [CI] 1.16-1.87) risk of osteopenia or osteoporosis. In case of blood cadmium, the risk for osteopenia or osteoporosis increased 2.1 times (95% CI 1.64-2.68).ConclusionsWe observed a significant association between blood heavy metals (lead and cadmium) levels and low BMD. Our findings suggest that heavy metal exposure may be a risk factor for osteoporosis.
| S-EPMC5153379 | biostudies-literature
Project description:UNLABELLED:New models describing anthropometrically adjusted normal values of bone mineral density and content in children have been created for the various measurement sites. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters. INTRODUCTION:Previous descriptions of children's bone mineral measurements by age have focused on segmenting diverse populations by race and sex without adjusting for anthropometric variables or have included the effects of a single anthropometric variable. METHODS:We applied multivariate semi-metric smoothing to the various pediatric bone-measurement sites using data from the Bone Mineral Density in Childhood Study to evaluate which of sex, race, age, height, weight, percent body fat, and sexual maturity explain variations in the population's bone mineral values. By balancing high adjusted R(2) values with clinical needs, two models are examined. RESULTS:At the spine, whole body, whole body sub head, total hip, hip neck, and forearm sites, models were created using sex, race, age, height, and weight as well as an additional set of models containing these anthropometric variables and percent body fat. For bone mineral density, weight is more important than percent body fat, which is more important than height. For bone mineral content, the order varied by site with body fat being the weakest component. Including more anthropometrics in the model reduces the overlap of the critical groups, identified as those individuals with a Z-score below -2, from the standard sex, race, and age model. CONCLUSIONS:If body fat is not available, the simpler model including height and weight should be used. The inclusion of multiple explanatory variables in the models provides the opportunity to calculate Z-scores that are adjusted with respect to the relevant anthropometric parameters.
| S-EPMC4768717 | biostudies-literature
Project description:IntroductionPreterm infants are at increased risk of osteopenia of prematurity due to insufficient bone mineral accretion. Data on long term effects of prematurity on bone health are conflicting. This study aimed to compare bone mineral density (BMD) in young adults born very preterm and full-term controls and to examine factors associated with long-term bone health.MethodsThis observational cross-sectional study enrolled 101 young adults (18-29?years) born <29?weeks of gestation and 95 sex- and age-matched full-term controls. Participants underwent dual-energy X-ray absorptiometry to measure areal BMD and body composition. Generalized estimated equations were used to compare groups adjusting for height Z-score, lean body mass and fat mass.ResultsAdults born preterm were shorter and lighter than full-term controls. Areal BMD was reduced at the lumbar spine, the femoral neck and whole body in the preterm versus full-term group, but after adjustment, areal BMD Z-score was only significantly lower at the femoral neck by -0.3 unit (95% confidence interval -0.6 to -0.0). Low BMD (Z-score???-1 standard deviation) at any site was observed in 53% of adults born preterm versus 28% of full-term controls, but this was not statistically significantly different. We did not identify any neonatal factors associated with lower BMD within the preterm group.ConclusionsVery preterm birth is associated with lower areal BMD at the femoral neck in young adulthood, even after accounting for body size. Whether this will translate into higher risk of osteoporotic fractures later in life remains unknown.
| S-EPMC6319299 | biostudies-literature