Effects of parathyroid hormone on bone mass, bone strength, and bone regeneration in male rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is associated with increased skeletal fragility and impaired fracture healing. Intermittent PTH therapy increases bone strength; however, its skeletal and metabolic effects in diabetes are unclear. We assessed whether PTH improves skeletal and metabolic function in rats with T2DM.

Clinical and endocrine correlates of circulating sclerostin levels in patients with type 1 diabetes mellitus.

Aim: Type 1 diabetes mellitus (T1DM) increases fragility fractures due to low bone mass, micro-architectural alterations and decreased bone formation. Sclerostin is expressed by osteocytes and inhibits osteoblastic bone formation. We evaluated serum sclerostin levels in T1DM and their association with bone mineral density (BMD), bone turnover, glycaemic control and physical activity.

Metal hypersensitivity and metal ion levels in patients with coated or uncoated total knee arthroplasty: a randomised controlled study.

Purpose: Metal ion release by orthopaedic implants may cause local and systemic effects and induce hypersensitivity reactions. Coated implants have been developed to prevent or reduce these effects. This study was initiated to investigate the safety of a novel coating for total knee arthroplasty (TKA) implants.

Deconstructing vitamin D deficiency.

Vitamin D deficiency causes advanced aging of bone tissue with accumulation of microcracks (Busse et al., this issue).

Correlates of bone microarchitectural parameters and serum sclerostin levels in men: the STRAMBO study.

Sclerostin is predominantly expressed by osteocytes. Serum sclerostin levels are positively correlated with areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) and bone microarchitecture assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in small studies. We assessed the relation of serum sclerostin levels with aBMD and microarchitectural parameters based on HR-pQCT in 1134 men aged 20 to 87 years using multivariable models adjusted for confounders (age, body size, lifestyle, comorbidities, hormones regulating bone metabolism, muscle mass and strength).

Trabectedin in the neoadjuvant treatment of high-grade pleomorphic sarcoma: report of a rare case and literature review.

Background. Pleomorphic sarcoma is an aggressive soft tissue sarcoma. In patients with high-risk extremity sarcomas, the significant survival benefits conferred by an intense regimen of neoadjuvant chemoradiotherapy and surgery were reported.

Sclerostin antibody treatment improves bone mass, bone strength, and bone defect regeneration in rats with type 2 diabetes mellitus.

Type 2 diabetes mellitus results in increased risk of fracture and delayed fracture healing. ZDF fa/fa rats are an established model of type 2 diabetes mellitus with low bone mass and delayed bone healing. We tested whether a sclerostin-neutralizing antibody (Scl-AbVI) would reverse the skeletal deficits of diabetic ZDF rats.

Skeletal and extraskeletal actions of denosumab.

Osteoclasts and osteoblasts define skeletal mass, structure and strength through their respective actions in resorbing and forming bone. This remodeling process is orchestrated by the actions of hormones and growth factors, which regulate a cytokine system comprising the receptor activator of nuclear factor κB ligand (RANKL), its receptor RANK and the soluble decoy receptor osteoprotegerin (OPG). Bone resorption depends on RANKL, which determines osteoclast formation, activity and survival.

Bone, sweet bone--osteoporotic fractures in diabetes mellitus.

Diabetes mellitus adversely affects the skeleton and is associated with an increased risk of osteoporosis and fragility fractures. The mechanisms underlying low bone strength are not fully understood but could include impaired accrual of peak bone mass and diabetic complications, such as nephropathy. Type 1 diabetes mellitus (T1DM) affects the skeleton more severely than type 2 diabetes mellitus (T2DM), probably because of the lack of the bone anabolic actions of insulin and other pancreatic hormones.

The osteoclast-associated receptor (OSCAR) is a novel receptor regulated by oxidized low-density lipoprotein in human endothelial cells.

Cross talks between the vascular and immune system play a critical role in vascular diseases, in particular in atherosclerosis. The osteoclast-associated receptor (OSCAR) is a regulator of osteoclast differentiation and dendritic cell maturation. Whether OSCAR plays a role in vascular biology and has an impact on atherogenic processes provoked by proinflammatory stimuli is yet unknown.

Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet.

Denosumab for bone diseases: translating bone biology into targeted therapy.

Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption.

From bone to breast and back - the bone cytokine RANKL and breast cancer.

Receptor activator of nuclear factor-κB ligand (RANKL) plays a pivotal role in regulating bone homeostasis. Osteoporosis and malignant bone disease secondary to breast cancer are characterized by enhanced RANKL production and increased bone turnover. Thus, denosumab, a monoclonal antibody to RANKL, has been developed and is now approved for various bone loss conditions.

Seizures associated with zoledronic acid for osteoporosis.

Context: Bisphosphonates represent potent antiresorptive drugs that are established for therapy of patients with benign and malignant bone diseases. Zoledronic acid is an iv aminobisphosphonate that is administered annually against osteoporosis. Because of its potency and the parenteral route of administration, zoledronic acid is an alternative to oral bisphosphonates, in particular in elderly patients with multiple comorbidities.

Expression profile of WNT molecules in prostate cancer and its regulation by aminobisphosphonates.

Skeletal metastases represent a frequent complication in patients with advanced prostate cancer (PCa) and often require bisphosphonate treatment to limit skeletal-related events. Metastasized PCa cells disturb bone remodeling. Since the WNT signaling pathway regulates bone remodeling and has been implicated in tumor progression and osteomimicry, we analyzed the WNT profile of primary PCa tissues and PCa cell lines and assessed its regulation by bisphosphonates.

Approach to the patient with secondary osteoporosis.

Secondary osteoporosis is characterized by low bone mass with microarchitectural alterations in bone leading to fragility fractures in the presence of an underlying disease or medication. Scenarios that are highly suspicious for secondary osteoporosis include fragility fractures in younger men or premenopausal women, very low bone mineral density (BMD) values, and fractures despite anti-osteoporotic therapy. An open-minded approach with a detailed history and physical examination combined with first-line laboratory tests are aimed at identifying clinical risk factors for fractures, osteoporosis-inducing drugs, and underlying endocrine, gastrointestinal, hematologic, or rheumatic diseases, which then need to be confirmed by specific and/or more invasive tests.

Multimodal therapy for vertebral involvement of systemic mastocytosis.

Study Design: Case report and clinical discussion.

Objective: To describe a rare case of vertebral involvement of systemic mastocytosis and its multimodal therapy.

Summary Of Background Data: Vertebral fractures in young men are rare events.

Does combined imaging of the pre- and postsynaptic dopaminergic system increase the diagnostic accuracy in the differential diagnosis of parkinsonism?

Purpose: We hypothesized that combining pre- and postsynaptic quantitative information about the dopaminergic system would provide a higher diagnostic accuracy in the differential diagnosis of parkinsonism than specific striatal D(2) receptor binding alone. Therefore, the aim of the study was to introduce new semi-quantitative parameters and evaluate their ability to discriminate between Parkinson's disease (IPS) and non-idiopathic parkinsonian syndromes (non-IPS).

Methods: In 100 patients (69 IPS, 31 non-IPS), postsynaptic [(123)I]IBZM and presynaptic [(123)I]FP-CIT SPECT scans were evaluated by observer-independent techniques.

Extended studies of the striatal uptake of 99mTc-NC100697 in healthy volunteers.

Unlabelled: This study evaluates a new formulation of a (99m)Tc-labeled tropane derivate, (99m)Tc-NC100697, in a human volunteer study.

Methods: Eighty healthy subjects (39 females, 41 males) underwent MRI and SPECT (injected dose [mean +/- SD], 10.6 +/- 1.

Is iterative reconstruction an alternative to filtered backprojection in routine processing of dopamine transporter SPECT studies?

Unlabelled: In general, striatal dopamine transporter (DAT) binding is assessed by use of data reconstructed by filtered backprojection (FBP). The aim of this study was to investigate whether the use of an iterative reconstruction algorithm (ordered-subset expectation maximization [OSEM]) may provide results comparable to or even better than those obtained by standard FBP.

Methods: In 50 patients with parkinsonian syndromes, SPECT scans were acquired 4 h after injection of 185 MBq of (123)I-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ((123)I-FP-CIT) by use of a triple-head gamma-camera fitted with low-energy, high-resolution fanbeam collimators.

SERT and DAT availabilities under citalopram treatment in obsessive-compulsive disorder (OCD).

Serotonin and dopamine transporter (SERT, DAT) availabilities have prospectively been investigated using [123I]beta-CIT and single photon emission computed tomography in subjects with obsessive-compulsive disorder under treatment with the selective serotonin reuptake inhibitor citalopram. SERT availability decreased by a mean 36.5%, whereas DAT availability increased by about 40%.

Clinical testing of an optimized software solution for an automated, observer-independent evaluation of dopamine transporter SPECT studies.

Unlabelled: A lack of standardized evaluation procedures for dopamine transporter (DAT) SPECT investigations impairs both intra- and interindividual comparisons as well as multicenter trials-for example, for assessment of disease progression or the response to various drug treatments. Therefore, the aim of this study was to evaluate a novel automated method, which has been specifically developed for a standardized quantification of N-(3-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane (123I-FP-CIT) SPECT studies.

Methods: DAT binding ratios of 155 (123)I-FP-CIT SPECT studies in 14 control subjects and 141 patients referred to confirm or exclude a presynaptic dopaminergic deficit were determined manually and by a fully automated technique.