Autosomal Recessive Osteogenesis Imperfecta Caused by a Novel Homozygous COL1A2 Mutation

Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by brittle bones and extraskeletal manifestations. The disease phenotype varies greatly. Most commonly, OI arises from monoallelic mutations in one of the two genes encoding type I collagen, COL1A1 and COL1A2 and is inherited as an autosomal dominant trait. Here, we describe a consanguineous family with autosomal recessive OI caused by a novel homozygous glycine substitution in COL1A2, NM_000089.3: c.604G > A, p.(Gly202Ser), detected by whole-genome sequencing. The index patient is a 31-year-old Greek woman with severe skeletal fragility. She had mild short stature, low bone mineral density of the lumbar spine and blue sclerae. She had sustained multiple long bone and vertebral fractures since childhood and had been treated with bisphosphonates for several years. She also had an affected sister with similar clinical manifestations. Interestingly, the parents and one sister, all carriers of the COL1A2 glycine mutation, did not have manifestations of OI. In summary, we report on autosomal recessive OI caused by a homozygous glycine-to-serine substitution in COL1A2, leading to severe skeletal fragility. The mutation carriers lacked OI manifestations. This family further expands the complex genetic spectrum of OI and underscores the importance of genetic evaluation for correct genetic counselling.Peer reviewe

Sequential treatment with teriparatide and strontium ranelate in a postmenopausal woman with atypical femoral fractures after long-term bisphosphonate administration

AbstrAct ObJEctIVE: Despite the existence of numerous case series, no evidenced-based medical management for atypical fractures associated with bisphosphonate (bP) treatment has been established. DEsIGN: We report the outcome of teriparatide (trP) administration followed by strontium ranelate (sr) in a woman with a complete and an incomplete contralateral atypical fracture of the femoral diaphysis (AFF) associated with bP treatment. the spontaneous complete AFF was managed with intramedullary nailing, discontinuation of bP and initiation trP. rEsULts: Eleven months later, she suffered a contralateral incomplete AFF. At the completion of the trP treatment, she had only slight discomfort in the femur with the incomplete AFF. bMD testing revealed increase of 7.61% at the lumbar spine (Ls) and 0.8% at the hip. Following trP, 1-year sr treatment resulted in further bMD increase of 9.2% at the Ls and 1.4% in the hip, while she does not report any pain. bone markers remain within the normal range. cONcLUsION: Our case indicates that sequential therapy with trP and sr in cases of AFF might be a rational treatment option. However, there is a need for additional information concerning the effect of trP and sr, given alone or sequentially, in these patients in order to incorporate these drugs into the management of AFF

Mosaic Deletions of Known Genes Explain Skeletal Dysplasias With High and Low Bone Mass

Mosaicism, a state in which an individual has two or more genetically distinct populations of cells in the body, can be difficult to detect because of either mild or atypical clinical presentation and limitations in the commonly used detection methods. Knowledge of the role of mosaicism is limited in many skeletal disorders, including osteopathia striata with cranial sclerosis (OSCS) and cleidocranial dysplasia (CCD). We used whole-genome sequencing (WGS) with coverage >40x to identify the genetic causes of disease in two clinically diagnosed patients. In a female patient with OSCS, we identified a mosaic 7-nucleotide frameshift deletion in exon 2 of AMER1, NM_152424.4:c.855_861del:p.(His285Glnfs*7), affecting 8.3% of the WGS reads. In a male patient with CCD, approximately 34% of the WGS reads harbored a 3710-basepair mosaic deletion, NC_000006.11:g.45514471_45518181del, starting in intron 8 of RUNX2 and terminating in the 3 ' untranslated region. Droplet digital polymerase chain reaction was used to validate these deletions and quantify the absolute level of mosaicism in each patient. Although constitutional variants in AMER1 and RUNX2 are a known cause of OSCS and CCD, respectively, the mosaic changes here reported have not been described previously. Our study indicates that mosaicism should be considered in unsolved cases of skeletal dysplasia and should be investigated with comprehensive and sensitive detection methods. (c) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.Peer reviewe

A multicenter study to evaluate harmonization of assays for N-terminal propeptide of type I procollagen (PINP): a report from the IFCC-IOF Joint Committee for Bone Metabolism

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Adipose Tissue Lipolysis Is Upregulated in Lean and Obese Men During Acute Resistance Exercise

OBJECTIVE—To investigate the effect of acute resistance exercise on adipose tissue triacylglycerol lipase activity (TGLA) in lean and obese men

Intensity of Resistance Exercise Determines Adipokine and Resting Energy Expenditure Responses in Overweight Elderly Individuals

OBJECTIVE - To evaluate the time course of leptin, adiponectin, and testing energy expenditure (REE) responses in overweight elderly mates after acute resistance exercise protocols of various intensity configurations. RESEARCH DESIGN AND METHODS - Forty inactive men (65-82 years) were randomly assigned to one of four groups (n = 10/group): control, low-intensity resistance exercise, moderate-intensity resistance exercise, and high-intensity resistance exercise. Exercise energy cost, REE, leptin, adiponectin, cortisol, insulin, lactate, glucose, nonesterified fatty acids (NEFAs), and glycerol were determined at baseline, immediately after exercise, and during a 72-h recovery period. RESULTS - Exercise energy cost was lower in high-intensity than in low-intensity and moderate-intensity groups (221.6 +/- 8.8 vs. 295.6 +/- 10.7 and 281.6 +/- 9.8 kcal, P < 0.001). Lactate, glucose, NEFAs, and glycerol concentrations increased (P < 0.001) after exercise and returned to baseline thereafter in all groups. REE increased (P < 0.001) in all groups at 12 h in an intensity-dependent manner (P < 0.05). REE reached baseline after 48 h in the low- and mode rate-intensity groups and after 72 h in the high-intensity group. Cortisol peaked in all active groups after exercise (P < 0.001) and remained elevated (P < 0.001) for 12 h. After adjustment for plasma volume shifts, leptin remained unaltered. Adiponectin concentration increased after 12 hand remained elevated for 24 h only in the high-intensity group (P < 0.001). CONCLUSIONS - Resistance exercise does not alter circulating leptin concentration but does increase REE and adiponectin in an intensity-dependent manner for as long as 48 and 24 h, respectively, in overweight elderly individuals. It appears that resistance exercise may represent an effective approach for weight management and metabolic control in overweight elderly individuals

Circulating Sclerostin responses to acute weight and non weight bearing sport activity in pre adolescent males

Mechanical loading, i.e. physical activity and/or exercise, promotes bone formation during growth. Sclerostin, a glycoprotein, mediates osteocytes' response to mechanical loading by inhibiting the Wnt/lf-catenin pathway thereby inhibiting bone formation.Published versio

Les indices du Beaujolais meridional et les alterations qui y sont associees: comparaison avec le secteur de la Brevenne

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 78475 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc