41 research outputs found
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
Normal bone turnover markers in a patient with active Paget’s disease of bone: response to treatment with zoledronic acid
Celem leczenia choroby kości Pageta (PDB) jest zahamowanie zwiększonego obrotu kostnego. Obecnie lekami z wyboru są bisfosfoniany.
Do wskazań do stosowania leków antyresorpcyjnych u pacjentów z objawowa postacią PDB należą: bóle kostne i stawowe, powikłania
neurologiczne, planowany zabieg chirurgiczny w rejonie aktywnych zmian chorobowych i hiperkalcemia spowodowana unieruchomieniem.
Celem terapii antyresorpcyjnej jest uzyskanie poprawy stanu klinicznego i remisji biochemicznej, ocenianej na podstawie
normalizacji stężeń biomarkerów obrotu kostnego. Przed podjęciem decyzji o wdrożeniu terapii u chorych w późnej, sklerotycznej fazie
choroby (burned out) należy wziąć pod uwagę pogorszenie stanu klinicznego, a zwłaszcza występowanie bólów kostnych. U tych chorych
duże znaczenie ma badanie scyntygraficzne kości, ponieważ może ono uwidocznić zwiększoną aktywność osteoblastyczną, której mogą
nie wykazać markery obrotu kostnego. W niniejszej pracy przedstawiono przypadek chorego w późnym, sklerotycznym stadium PDB,
u którego występowały nasilone objawy kliniczne, lecz stężenia markerów obrotu kostnego były prawidłowe. Po leczeniu kwasem zoledronowym
nastąpiła istotna poprawa kliniczna.The treatment of Paget’s disease of bone (PDB) aims at the suppression of abnormal bone turnover; bisphosphonates are currently the
treatment of choice. Indications for antiresorptive treatment in symptomatic patients with PDB include bone or joint pain, neurological
complications, surgery planned at an active pagetic site and hypercalcaemia from immobilisation. The goals of antiresorptive treatment
are clinical improvement and biochemical remission, as assessed by the normalisation of bone turnover markers. Clinical deterioration,
especially bone pain, should be considered before deciding to treat patients with late sclerotic (burned-out) PDB. Bone scintigraphy may
be of importance in these patients, because it depicts increased osteoblastic activity, when bone markers may not. We present a case of
late sclerotic PDB with clinical deterioration but normal bone turnover markers, who experienced significant clinical improvement after
treatment with zoledronic acid
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
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
Is Serum IL-17A a Useful Systemic Biomarker in Patients With Langerhans Cell Histiocytosis?
RANKL inhibition for the management of patients with benign metabolic bone disorders
The receptor activator of NF-kappa B ligand (RANKL) is a member of the
TNF receptor superfamily, essential for osteoclastogenesis. It binds to
its receptor activator of NF-kappa B on the surface of osteoclast
precursors and enhances their differentiation, survival and fusion,
while it activates mature osteoclasts and inhibits their apoptosis. The
effects of RANKL are counteracted by osteoprotegerin (OPG), a
neutralizing decoy receptor. Derangement of the balance in RANKL/OPG
action is implicated in the pathophysiology of metabolic bone diseases,
including osteoporosis. Current therapies used to prevent or treat
metabolic bone diseases are thought to act, at least in part, through
modification of the RANKL/OPG dipole. The idea of using a molecule that
could specifically bind and neutralize RANKL to decrease bone resorption
and subsequent bone loss is appealing. Recombinant OPG was initially
tested. Denosumab, a fully human monoclonal antibody against RANKL, is a
promising antiresorptive agent under investigation. it rapidly decreases
bone turnover markers resulting in a significant increase in bone
mineral density and reduction in fracture risk. However, because
receptor activator of NF-kappa B activation by RANKL is also essential
for T-cell growth and dendritic-cell function, inhibition of its action
could simultaneously affect the immune system, leading to susceptibility
in infections or malignancies
Reduced bone mineral density in adult patients with Langerhans cell histiocytosis
This retrospective study evaluated bone mineral density (BMD) and bone
turnover in adults with LCH. Twenty-five adult patients and 25 matched
controls were evaluated with BMD measurement and indices of bone
metabolism. A BMD value below the expected range for age (Z-score
<==-2.0) was found in 20% of patients; in particular, all
postmenopausal women and men over 50-years had either osteoporosis or
osteopenia. Patients with active disease had significantly lower
Z-scores compared to patients with inactive disease and controls.
Reduced bone turnover was found in all 14 patients treated with
chemotherapy. No fractures due to osteoporosis were identified during
305.15 patient-years of follow-up. Pediatr Blood Cancer 2012; 58:
819822. (C) 2011 Wiley Periodicals, Inc
The three-year effect of a single zoledronate infusion on bone mineral density and bone turnover markers following denosumab discontinuation in women with postmenopausal osteoporosis
Irisin and Bone in Sickness and in Health: A Narrative Review of the Literature
Irisin is a hormone-like myokine produced by the skeletal muscle in response to exercise. Upon its release into the circulation, it is involved in the browning process and thermogenesis, but recent evidence indicates that this myokine could also regulate the functions of osteoblasts, osteoclasts, and osteocytes. Most human studies have reported that serum irisin levels decrease with age and in conditions involving bone diseases, including both primary and secondary osteoporosis. However, it should be emphasized that recent findings have called into question the importance of circulating irisin, as well as the validity and reproducibility of current methods of irisin measurement. In this review, we summarize data pertaining to the role of irisin in the bone homeostasis of healthy children and adults, as well as in the context of primary and secondary osteoporosis. Additional research is required to address methodological issues, and functional studies are required to clarify whether muscle and bone damage per se affect circulating levels of irisin or whether the modulation of this myokine is caused by the inherent mechanisms of underlying diseases, such as genetic or inflammatory causes. These investigations would shed further light on the effects of irisin on bone homeostasis and bone disease