41 research outputs found
Bone metabolism in Langerhans cell histiocytosis
Langerhans cell histiocytosis (LCH) is a rare disease of not well-defined etiology that involves immune cell activation and frequently affects the skeleton. Bone involvement in LCH usually presents in the form of osteolytic lesions along with low bone mineral density. Various molecules involved in bone metabolism are implicated in the pathogenesis of LCH or may be affected during the course of the disease, including interleukins (ILs), tumor necrosis factor α, receptor activator of NF-κB (RANK) and its soluble ligand RANKL, osteoprotegerin (OPG), periostin and sclerostin. Among them IL-17A, periostin and RANKL have been proposed as potential serum biomarkers for LCH, particularly as the interaction between RANK, RANKL and OPG not only regulates bone homeostasis through its effects on the osteoclasts but also affects the activation and survival of immune cells. Significant changes in circulating and lesional RANKL levels have been observed in LCH patients irrespective of bone involvement. Standard LCH management includes local or systematic administration of corticosteroids and chemotherapy. Given the implication of RANK, RANKL and OPG in the pathogenesis of the disease and the osteolytic nature of bone lesions, agents aiming at inhibiting the RANKL pathway and/or osteoclastic activation, such as bisphosphonates and denosumab, may have a role in the therapeutic approach of LCH although further clinical investigation is warranted
Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab
Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), a member of the tumor necrosis factor receptor superfamily essential for osteoclastogenesis. Denosumab treatment is associated with a rapid, sustained, and reversible reduction in bone turnover markers, a continuous marked increase in bone mineral density at all sites, and a marked decrease in the risk of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis. Therefore, it could be considered as an effective alternative to previous bisphosphonate treatment as well as first-line treatment of severe osteoporosis. Cost-effectiveness studies support this suggestion. In addition, denosumab seems to be the safest treatment option in patients with impaired renal function. Denosumab is characterized by reversibility of its effect after treatment discontinuation, in contrast with bisphosphonates. Large-scale clinical trials, including the extension of FREEDOM trial for up to 5 years, are reassuring for its safety. However, given its brief post-market period, vigilance regarding adverse events related to putative RANKL inhibition in tissues other than bone, as well as those related to bone turnover oversuppression, is advised
Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net
Investigational anabolic agents for the treatment of osteoporosis: an update on recent developments
Introduction: Teriparatide, a PTH analogue, was the first anabolic agent
to be approved for the treatment of osteoporosis in 2002. Abaloparatide
was also recently approved by the FDA. The need for other anabolic
agents is still unmet.
Areas covered: In this review, we discuss target molecules and recent
advances in the field of anabolic therapy for osteoporosis. PTH and
PTHrP analogues binding to the PTH receptor and different routes of
administration of teriparatide to avoid the burden of daily subcutaneous
injections are discussed. We also review antibodies targeting
suppressors of the Wnt pathway such as sclerostin and Dickopff-1.
Expert opinion: The development of alternative ways of administering PTH
receptor ligands is a promising field, especially via the transdermal
route. Other more promising molecules are still at very early stages of
development. FDA recently requested more data on Romosozumab
The annual incidence of Langerhans cell histiocytosis among adults living in Greece
Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid
neoplasia with a variable clinical course and outcome. Although there
are some data regarding its incidence in children, such information in
adults is lacking. To address the actual annual LCH incidence among
adults, we prospectively recorded, during a 12-month period, any new
case with a definitive histological diagnosis of LCH, among persons aged
18 and older living in Greece. Fourteen new cases were recorded
corresponding to an annual incidence of 1.58 per million population.
Female to male ratio was 1.34, and mean age at diagnosis was 43.5 years
Bone turnover markers in gingival crevicular fluid and blood serum of patients with fixed orthodontic appliances.
AIM
Bone remodelling can be followed through the bone turnover markers (BTMs). Aim of the present study was to record the fluctuation of an osteoclastic and an osteoblastic BTM [C-terminal telopeptide of type I collagen (CTX) and N-terminal pro-peptide of type I pro-collagen (PINP), respectively] in both the gingival crevicular fluid (GCF) and the serum of orthodontic patients before and after the initial application of orthodontic forces.
MATERIALS AND METHODS
Twenty-one Caucasian patients were prospectively evaluated. GCF and blood samples were collected in order to measure the selected biomarkers by ELISA at three time-points: exactly before, 5 days, and 14 days after bonding of the appliances. Standardized sample handling and patient preparation procedures were adopted in order to reduce pre-analytical variability.
RESULTS
GCF and serum CTX levels were found to be independent of age, although higher in the serum of female subjects. PINP levels were found higher in the serum of patients ≥25 years old, as well as in the GCF of males. A positive correlation between serum and GCF baseline PINP levels was observed.
LIMITATIONS
The effect of orthodontic treatment on bone remodelling might not be absolutely representative of the local bone microenvironment as the levels of the specific BTMs where measured within the GCF of the lower front teeth.
CONCLUSIONS
This is the first time PINP and CTX have been evaluated in the GCF and serum of orthodontic patients with fixed appliances. No statistically significant alterations of CTX and PINP levels in the GCF and the serum of patients were recorded over time during the initial stages of orthodontic treatment