Denosumab improves bone mineral density and microarchitecture and reduces bone pain in women with osteoporosis with and without glucocorticoid treatment. Petranova Tzvetanka,Sheytanov Ivan,Monov Simeon,Nestorova Rodina,Rashkov Rasho Biotechnology, biotechnological equipment Osteoporosis is a key health problem in postmenopausal women with high social and economic impact. Decreased bone mineral density (BMD) and deterioration of bone microarchitecture may occur also as a result of long-term glucocorticoid treatment (GCT) of autoimmune or inflammatory conditions. Denosumab specifically inhibits the binding of the receptor activator of nuclear factor-κB to its ligand, thus preventing osteoclast activation and bone resorption. The efficacy and safety of denosumab, administered subcutaneously as 60 mg, once every six months for 12 months, were evaluated in 60 patients with postmenopausal osteoporosis (PMO) divided into two groups. The GCT group included 30 patients receiving concomitant glucocorticoid therapy and the non-GCT group included 30 patients that did not receive GCT. In the non-GCT group, the 12-month treatment with denosumab resulted in BMD increase of 6.1% and 2.8% in lumbar spine and hip, respectively. T-score increased by 13.1% and 5.6% in both, the lumbar spine and hip. A slight rise in the Trabecular Bone Score (TBS) of 0.3% was observed. Bone pain was markedly reduced by 56.2%. In the GCT group, denosumab therapy increased BMD with 5.8% and 2.3% in lumbar spine and hip, respectively. T-score of lumbar spine and hip significantly increased by 14.0% and 4.4%, and the TBS rose by 5%. Bone pain was reduced by 53.6%. These data confirm the available knowledge on denosumab efficacy and safety in women with PMO and also provide new insights into its therapeutic potential in patients with osteoporosis related to a long-term corticosteroid treatment. 10.1080/13102818.2014.967827

Denosumab and alendronate treatment in patients with back pain due to fresh osteoporotic vertebral fractures. Tetsunaga Tomoko,Tetsunaga Tomonori,Nishida Keiichiro,Tanaka Masato,Sugimoto Yoshihisa,Takigawa Tomoyuki,Takei Yoshitaka,Ozaki Toshifumi Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association INTRODUCTION:Denosumab specifically inhibits the receptor activator for nuclear factor-kappa B ligand (RANKL), and prevents osteoporotic fractures. Several reports have analyzed the effects of denosumab and alendronate alone on bone mineral density (BMD) or reduction of fracture risk. The objective of this study was to analyze the effects of antiresorptive osteoporosis pharmacotherapy on pain relief in patients with fresh vertebral fracture. METHODS:This retrospective, single-center study included 80 patients (10 males, 70 females) with fresh osteoporotic vertebral fractures treated using denosumab at a dose of 60 mg subcutaneously every 6 months (40 patients) or alendronate at a dose of 35 mg orally every week (40 patients) for 6 months in our hospital. The mean age of subjects was 77 years (range, 55-92 years). The primary outcome was duration of back pain. Secondary outcomes included changes in BMD, serum type 1 collagen cross-linked N-telopeptide (NTX), and serum N-terminal propeptide of type 1 collagen (P1NP) from baseline to 6 months. Pain catastrophizing due to back pain was assessed using the Pain Catastrophizing Scale (PCS). The incidences of further vertebral fracture and adverse events were also assessed. RESULTS:Pain relief was obtained at a mean of 3.3 weeks with denosumab and 5.4 weeks with alendronate. Pain relief was achieved significantly earlier with denosumab than with alendronate. At 6 months, change in BMD was higher with denosumab (6.1%) than with alendronate (0.8%). No significant differences in changes in NTX and P1NP were observed between groups. Scores for PCS were significantly lower for denosumab than for alendronate. The incidence of further vertebral fractures was 5% with denosumab and 10% with alendronate. Adverse event rates were similar between groups. CONCLUSIONS:Denosumab enabled earlier pain relief than alendronate and avoided catastrophizing in patients with osteoporotic vertebral fractures after 6 months of treatment. 10.1016/j.jos.2016.11.017

Effectiveness of denosumab on back pain-related disability and quality-of-life in patients with vertebral fragility fractures. Moretti Antimo,de Sire Alessandro,Curci Claudio,Toro Giuseppe,Gimigliano Francesca,Iolascon Giovanni Current medical research and opinion Denosumab is a fully human IgG2 monoclonal antibody that, neutralizing the receptor activator of nuclear factor kappa-Β ligand (RANKL), inhibits the osteoclast-mediated bone resorption. It is yet to be defined if denosumab can reduce osteoporosis-related disability and improve health-related quality-of-life (HRQoL) in patients with fragility fractures. To assess the effectiveness of denosumab in reducing back pain related disability and improving HRQoL in osteoporotic post-menopausal women with vertebral fractures. A real practice prospective study was carried out, enrolling women over 50 years with a post-menopausal osteoporosis that experienced at least one vertebral fracture receiving subcutaneous denosumab (60 mg, every 6 months), calcium carbonate (500-1000 mg/day) and cholecalciferol (800 IU/day) for 1 year. Back pain related disability was assessed as the primary outcome using the Spine Pain Index (SPI); secondary outcomes were: SF-12 (Physical Health Composite Score, PCS, and Mental Health Composite Score, MCS), and EuroQol-5D (EuroQol-5D-3L index and EuroQol-Visual Analog Scale, EQ-VAS). All outcome measures were assessed at baseline (T0), after 6 months (T1), and after 12 months (T2) of treatment. Trabecular Bone Score (TBS), lumbar spine (LS) and femoral neck (FN) BMD at T0 and T2 were also evaluated. This study included 140 post-menopausal women, mean age = 70.60 (SD = 8.81) years. There were statistically significant differences after 12 months (T2-T0) in all outcomes assessed: SPI ( < 0.001), SF-12 PCS ( < 0.001), SF-12 MCS ( < 0.001), EQ-5D-3L index ( = 0.039), and EQ-VAS ( = 0.003). Moreover, there was a significant improvement of both LS BMD ( < 0.001) and FN BMD ( < 0.001). No local or systemic adverse events, including new vertebral fractures, osteonecrosis of the jaw and atypical femur fractures, were reported. The data demonstrated that denosumab was effective in reducing back pain related disability and in improving HRQoL in post-menopausal women with vertebral fractures. 10.1080/03007995.2018.1545636

Chronic pain: an update on burden, best practices, and new advances. Cohen Steven P,Vase Lene,Hooten William M Lancet (London, England) Chronic pain exerts an enormous personal and economic burden, affecting more than 30% of people worldwide according to some studies. Unlike acute pain, which carries survival value, chronic pain might be best considered to be a disease, with treatment (eg, to be active despite the pain) and psychological (eg, pain acceptance and optimism as goals) implications. Pain can be categorised as nociceptive (from tissue injury), neuropathic (from nerve injury), or nociplastic (from a sensitised nervous system), all of which affect work-up and treatment decisions at every level; however, in practice there is considerable overlap in the different types of pain mechanisms within and between patients, so many experts consider pain classification as a continuum. The biopsychosocial model of pain presents physical symptoms as the denouement of a dynamic interaction between biological, psychological, and social factors. Although it is widely known that pain can cause psychological distress and sleep problems, many medical practitioners do not realise that these associations are bidirectional. While predisposing factors and consequences of chronic pain are well known, the flipside is that factors promoting resilience, such as emotional support systems and good health, can promote healing and reduce pain chronification. Quality of life indicators and neuroplastic changes might also be reversible with adequate pain management. Clinical trials and guidelines typically recommend a personalised multimodal, interdisciplinary treatment approach, which might include pharmacotherapy, psychotherapy, integrative treatments, and invasive procedures. 10.1016/S0140-6736(21)00393-7

Transition from acute to chronic pain after surgery. Glare Paul,Aubrey Karin R,Myles Paul S Lancet (London, England) Over the past decade there has been an increasing reliance on strong opioids to treat acute and chronic pain, which has been associated with a rising epidemic of prescription opioid misuse, abuse, and overdose-related deaths. Deaths from prescription opioids have more than quadrupled in the USA since 1999, and this pattern is now occurring globally. Inappropriate opioid prescribing after surgery, particularly after discharge, is a major cause of this problem. Chronic postsurgical pain, occurring in approximately 10% of patients who have surgery, typically begins as acute postoperative pain that is difficult to control, but soon transitions into a persistent pain condition with neuropathic features that are unresponsive to opioids. Research into how and why this transition occurs has led to a stronger appreciation of opioid-induced hyperalgesia, use of more effective and safer opioid-sparing analgesic regimens, and non-pharmacological interventions for pain management. This Series provides an overview of the epidemiology and societal effect, basic science, and current recommendations for managing persistent postsurgical pain. We discuss the advances in the prevention of this transitional pain state, with the aim to promote safer analgesic regimens to better manage patients with acute and chronic pain. 10.1016/S0140-6736(19)30352-6