Longitudinal Changes of Circulating miRNAs During Bisphosphonate and Teriparatide Treatment in an Animal Model of Postmenopausal Osteoporosis.

MicroRNAs regulate bone homeostasis, and circulating microRNAs have been proposed as novel bone biomarkers. The effect of anti-osteoporotic treatment on circulating microRNAs has not been described in detail. Therefore, we performed a comprehensive analysis of microRNA serum levels in ovariectomized (OVX) and sham-operated (SHAM) rats over 12 weeks of antiresorptive or osteoanabolic treatment.

Interplay between mineral crystallinity and mineral accumulation in health and postmenopausal osteoporosis.

Osteoporosis is characterized by an imbalance between bone formation and resorption rates, resulting in bone loss. For ethical reasons, effects of antiosteoporosis drugs are compared against patients receiving vitamin D and calcium supplementation which is a mild antiresorptive regimen. Bone formation may be resolved into two phases: the initial formation of mineral crystals (primary nucleation) and the subsequent mineral accumulation (secondary nucleation and mineral growth) on them.

New therapeutic options for bone diseases.

In recent years, new treatment options for both common and rare bone diseases have become available. The sclerostin antibody romosozumab is the most recently approved drug for the therapy of postmenopausal osteoporosis. Its anabolic capacity makes it a promising treatment option for severe osteoporosis.

Mineral and organic matrix composition at bone forming surfaces in postmenopausal women with osteoporosis treated with either teriparatide or zoledronic acid.

The ability of bone to resist fracture is dependent on the composite nature of its mineral and organic matrix content. Teriparatide (TPTD) and zoledronic acid (ZOL) are approved anabolic and antiresorptive therapies, respectively, to reduce fracture risk in women with postmenopausal osteoporosis. In the SHOTZ study, postmenopausal women with osteoporosis were treated with TPTD (20 μg daily, subcutaneous) or ZOL (5 mg/year, intravenous infusion) for 24 months.

Single high-dose peroral caffeine intake inhibits ultraviolet radiation-induced apoptosis in human lens epithelial cells in vitro.

Purpose: The aim of the present study was to determine whether caffeine concentrations in human lens epithelial cells (LECs) achieved from acute peroral caffeine intake inhibit ultraviolet radiation-induced apoptosis in vitro.

Methods: Patients were planned for cataract surgery of both eyes with a caffeine abstinence of 2 weeks in total, starting 1 week before surgery of the first eye. The second eye was scheduled 1 week after the first eye.

No Role of Osteocytic Osteolysis in the Development and Recovery of the Bone Phenotype Induced by Severe Secondary Hyperparathyroidism in Vitamin D Receptor Deficient Mice.

Osteocytic osteolysis/perilacunar remodeling is thought to contribute to the maintenance of mineral homeostasis. Here, we utilized a reversible, adult-onset model of secondary hyperparathyroidism to study femoral bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) based on quantitative backscattered electron imaging. Male mice with a non-functioning vitamin D receptor (VDR) or wild-type mice were exposed to a rescue diet (RD) (baseline) and subsequently to a low calcium challenge diet (CD).

Bone tissue material composition is compromised in premenopausal women with Type 2 diabetes.

Type 2 diabetes mellitus (T2DM) patients are at an increased risk of fracture despite normal to high bone mineral density (BMD) values. In this cross-sectional study we establish bone compositional properties in tetracycline labeled iliac crest biopsies from premenopausal women diagnosed with T2DM (N = 26). Within group comparisons were made as a function of tissue age (TA), presence of chronic complications (CC), glycosylated haemoglobin (HbA1c) levels, and morphometric fracture (MFx).

Osteoporosis Therapeutics 2020.

Numerous safe and efficient drug therapies are currently available to decrease risk of low trauma fractures in patients with osteoporosis including postmenopausal, male, and secondary osteoporosis. In this chapter, we give first an overview of the most important outcomes regarding fracture risk reduction, change in bone mineral density (BMD by DXA) and/or bone markers of the phase III clinical studies of well-established therapies (such as Bisphosphonates, Denosumab or Teriparatide) and also novel therapies (such as Romosozumab or Abaloparatide) and highlight their mechanisms of action at bone tissue/material level. The latter understanding is not only essential for the choice of drug, duration and discontinuation of treatment but also for the interpretation of the clinical outcomes (in particular of eventual changes in BMD) after drug administration.

Progressive Deformity of the Lower Limbs in a Patient with KID (Keratitis-Ichthyosis-Deafness) Syndrome.

Purpose: Progressive deformity of the lower limbs can be encountered in a long list of syndromic associations. The baseline tool in the management of such disorders is to approach to a definite diagnosis.

Methods: We describe a 4-year-old girl who presented with the clinical phenotype and genotype of congenital erythrokeratoderma, keratosis, and sensorineural hearing loss (keratitis-ichthyosis-deafness syndrome) (KID syndrome).

Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH).

X-linked hypophosphatemia (XLH) caused by PHEX mutations results in elevated serum FGF23 levels, renal phosphate wasting and low 1,25-dihydroxyvitamin D. The glycophosphoprotein osteopontin, a potent inhibitor of mineralization normally degraded by PHEX, accumulates within the bone matrix. Conventional therapy consisting of supplementation with phosphate and vitamin D analogs is burdensome and the effects on bone material poorly characterized.

No evidence for alteration in early secondary mineralization by either alendronate, teriparatide or combination of both in transiliac bone biopsy samples from postmenopausal osteoporotic patients.

The influence of treatment with alendronate (ALN), teriparatide (TPTD) or concurrent treatment with both on the human bone matrix mineralization has not yet been fully elucidated. For this purpose we analyzed quadruple fluorochrome labelled transiliac bone biopsy samples ( = 66) from postmenopausal osteoporotic women with prior and ongoing ALN (ALN-Rx arm) or without ALN (Rx-Naïve arm) after 7 months treatment with cyclic or daily TPTD or without TPTD using quantitative backscattered electron imaging and confocal scanning laser microscopy. Additionally to the bone mineralization density distribution (BMDD) of entire cancellous and cortical compartments, we measured the mineralization kinetics, i.

Inflammatory Bowel Disease: A Nationwide Study of Hip Fracture and Mortality Risk After Hip Fracture.

Background And Aims: With rising rates of inflammatory bowel diseases [IBD] in older adults, management of comorbidities such as osteoporosis is becoming increasingly important. Hip fracture [HF] is the most serious consequence of low bone mineral quality and is associated with excess risk of mortality. For older IBD patients, there are only limited data available.

Substitution of murine type I collagen A1 3-hydroxylation site alters matrix structure but does not recapitulate osteogenesis imperfecta bone dysplasia.

Null mutations in CRTAP or P3H1, encoding cartilage-associated protein and prolyl 3-hydroxylase 1, cause the severe bone dysplasias, types VII and VIII osteogenesis imperfecta. Lack of either protein prevents formation of the ER prolyl 3-hydroxylation complex, which catalyzes 3Hyp modification of types I and II collagen and also acts as a collagen chaperone. To clarify the role of the A1 3Hyp substrate site in recessive bone dysplasia, we generated knock-in mice with an α1(I)P986A substitution that cannot be 3-hydroxylated.

Newly formed and remodeled human bone exhibits differences in the mineralization process.

During human skeletal growth, bone is formed via different processes. Two of them are: new bone formation by depositing bone at the periosteal (outer) surface and bone remodeling corresponding to a local renewal of tissue. Since in remodeling formation is preceded by resorption, we hypothesize that modeling and remodeling could require radically different transport paths for ionic precursors of mineralization.