UNASSIGNED: Postmenopausal osteoporosis (PMOP) increases fracture risk in women. Though traditional treatments are slow to act, combining romosozumab with conventional therapy shows promise. Despite its growing use, studies on effectiveness are limited. This study aims to systematically evaluate the combined therapy\'s impact on pain relief, disease progression, and adverse reactions in PMOP patients.
UNASSIGNED: Databases including PubMed, EMBASE, ScienceDirect, and the Cochrane Library were searched from their inception to September 2023 to identify randomized controlled trials (RCTs) evaluating the role of romosozumab in PMOP. Random or fixed effect models were employed for statistical analysis. Two reviewers independently assessed the quality of the included studies and extracted the data. The meta-analysis was conducted using RevMan 5.4 software.
UNASSIGNED: Six RCTs with a total sample size of 17,985 cases were included. The incidence of vertebral fractures was compared and analyzed after 12 and 24 months of treatment. Romosozumab significantly reduced the incidence of vertebral fractures at 24 months (OR = 0.36; 95% CI: 0.35-0.52) but not at 12 months (OR = 0.39; 95% CI: 0.14-1.05). It was also associated with a decreased incidence of nonvertebral fractures (OR = 0.79; 95% CI: 0.66-0.94) and clinical fractures at 24 months (OR = 0.70; 95% CI: 0.59-0.82) compared to standard therapy. Romosozumab demonstrated a significant improvement in percentage change in bone mineral density (BMD) [mean difference (MD) = 10.38; 95% CI: 4.62-16.14] and in hip joint BMD (MD = 4.24; 95% CI: 2.92-5.56). There was no notable difference in adverse reactions compared to standard care (p > 0.05). Funnel plots displayed a predominantly symmetrical pattern, suggesting no evidence of publication bias in the selected literature.
UNASSIGNED: Combining romosozumab with conventional therapy effectively treats PMOP, significantly reducing vertebral, non-vertebral, and clinical fractures while increasing BMD in the hip, femoral neck, and lumbar spine. However, further high-quality studies are needed for validation.

UNASSIGNED: Romosozumab is a novel monoclonal antibody that binds to sclerostin, and has dual effects of increasing bone formation and decreasing bone resorption, giving it a unique mechanism of action. The objective of this study was to perform a systematic review and meta-analysis based on existing worldwide data on treatment effects and safety of romosozumab in randomized controlled trials.
UNASSIGNED: A systematic search was carried out on four databases including PubMed, Embase, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The keywords used for search was \"(romosozumab) AND (osteoporosis OR safety)\". Randomized controlled trial or post-hoc studies of the included randomized controlled trial which studied the effects and safety of romosozumab were included. The quality of selected studies was assessed with the Cochrane collaboration tool and the PEDro scale.
UNASSIGNED: 20 studies were included for qualitative analysis. 14 studies were included for meta-analysis. In total, there were 13,507 (n = 13,507) participants with 637 men and 12,870 women from original cohorts. The overall mean difference was in favor of romosozumab treatment for lumbar spine (10.04 (95 % confidence interval (CI) = 7.51-12.57; p < 0.00001)), total hip (4.04 (95 % CI = 3.10-4.99; p < 0.00001)) and femoral neck bone mineral density (3.77 (95 % CI = 2.90-4.64; p < 0.00001)) at 12 months. There was significantly less likelihood of new vertebral fractures with romosozumab compared to control (odds ratio (OR) 0.42 (95 % CI = 0.20-0.89); p = 0.02) at 12 months of treatment. There was significantly less likelihood of new vertebral fracture at 24 months with 12 months of romosozumab followed by sequential treatment with anti-resorptive compared to control with only anti-resorptive agent use (OR 0.36 (95 % CI = 0.18-0.71); p = 0.003). There was no significant difference in serious adverse events and fatal adverse events with use of romosozumab compared with control in our meta-analyses. There were no significant differences in serious cardiovascular events in Asian population of romosozumab with control group with 12 months of romosozumab treatment followed by 24 months of anti-resorptive agent with OR 1.09 (95 % CI = 0.40-2.96; P = 0.86). There was no significant difference between romosozumab group and control group for the median time to radiographic healing. Our qualitative analysis on Quantitative Computed Tomography (QCT), Finite element analysis (FEA) and bone biopsy analyses demonstrated that romosozumab improved parameters and measures in these domains as well.
UNASSIGNED: In conclusion, our study showed that romosozumab was an effective agent to treat osteoporosis with high quality evidence. There were no significant differences in the adverse events, serious adverse events, fatal adverse events identified. Further subgroup analysis of cardiovascular events and cardiovascular death in the total population showed no differences either.
UNASSIGNED: Given the results, romosozumab is an effective agent to treat patients with very-high risk of osteoporotic fractures.

Bone forming agents, also known as anabolic therapies, are essential in managing osteoporosis, particularly for patients at very high-risk of fractures. Identifying candidates who will benefit the most from these treatments is crucial. For example, this group might include individuals with severe osteoporosis, multiple vertebral fractures, a recent fragility fracture or those unresponsive to antiresorptive treatments. Definitions of patients with a very high fracture risk vary across nations, are often based on fracture history, bone mineral density (BMD), and/or fracture risk calculated by FRAX® or other algorithms. However, for very high-risk patients, anabolic agents such as teriparatide, abaloparatide, or romosozumab are commonly recommended as first-line therapies due to their ability to stimulate new bone formation and improve bone microarchitecture, offering significant benefits in rapid fracture reduction over antiresorptive therapies. The cost-effectiveness of these agents is a critical consideration for decision-makers. Despite their higher costs, their effectiveness in significantly reducing fracture risk and improving quality of life can justify the investment, especially when long-term savings from reduced fracture rates and associated healthcare costs are considered. Additionally, after completing a course of anabolic therapy, transitioning to antiresorptive agents like bisphosphonates or denosumab is crucial to maintain the gains in bone density and minimize subsequent fracture risks. This sequential treatment approach ensures sustained protection and optimal resource utilization. In summary, the effective use of bone forming agents in osteoporosis requires a comprehensive strategy that includes accurate patient identification, consideration of cost-effectiveness, and implementation of appropriate sequential treatments, ultimately maximizing patient outcomes and healthcare efficiency.

Hypophosphatasia is a rare inherited metabolic disease leading to inhibition of bone and teeth mineralization that can be complicated by multiple insufficiency fractures. Treatment is currently limited to enzyme replacement therapy using bone-targeting recombinant human alkaline phosphatase, or asfotase alfa. Romosozumab is a monoclonal anti-sclerostin antibody originally indicated for the treatment of osteoporosis in postmenopausal women with high-risk of fracture. Recently its indication had been expanded to other metabolic bone disorders such as osteogenesis imperfecta. We report a unique case of a 67-yer-old female with hypophosphatasia complicated by multiple delayed-union and nonunion insufficiency fractures of the pelvis. After 12-month therapy with Romosozumab to address her osteoporosis, the patient healed her fractures and increased her bone mass density. Our case report shows interesting effects of Romozumab in an adult patient with hypophosphatasia. It not only helped increase bone density, but also help in the healing process of delayed-union and nonunion insufficiency fractures of the pelvis and prevented the occurrence of new fractures during the treatment period. To our knowledge, this is the first report describing the potential effect of Romosozumab on insufficiency fractures in patients with hypophosphatasia.

UNASSIGNED: There are challenges for the treatment of osteoporosis in patients with kidney failure and monoclonal antibodies (MAb) might be a suitable therapy. However, the efficacy and safety of MAb among patients with osteoporosis and renal insufficiency remains unclear.
UNASSIGNED: We systematically searched PubMed, Embase, and Cochrane Central for studies evaluating the efficacy and safety of the use of MAb in patients with osteoporosis and renal insufficiency. We pooled risk ratios (RR) and 95% confidence intervals (CI) for binary outcomes. Mean difference (MD) was used for continuous outcomes.
UNASSIGNED: We included 5 studies with 33,550 patients. MAb therapy decreased the risk of vertebral fractures (RR 0.32; 95% CI 0.26-0.40; P < 0.01) when compared to placebo and no statistical difference was found when comparing to bisphosphonate (RR 0.71; 95% CI 0.49-1.03; P = 0.07). MAb therapy also decreased the risk of nonvertebral fractures (RR 0.79; 95% CI 0.69-0.91; P = 0.0009). Lumbar spine bone mineral density (BMD) was higher in the MAb therapy when compared to both placebo (MD 10.90; 95% CI 8.00-13.80; P < 0.01) and bisphosphonate (MD 7.66; 95% CI 6.19-9.14; P < 0.01). There was no statistically significant difference in the change of estimated glomerular filtration rate and in the incidence of hypocalcemia and serious adverse events between groups.
UNASSIGNED: There were reductions in both vertebral and nonvertebral fracture risks, alongside improvements in BMD among patients with renal insufficiency treated with MAb.

This multicentre, prospective cohort study measured the effect of romosozumab for 12 months on bone mineral density, taking into account prior therapies. Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip.
BACKGROUND: In Switzerland, romosozumab is administered to high-risk osteoporosis patients. Our study aimed to assess the effect of romosozumab on bone mineral density (BMD), taking into account prior therapies.
METHODS: This multicentre, prospective cohort study measured the effect of romosozumab for 12 months in patients in a nationwide Swiss osteoporosis registry. BMD and bone turnover marker (P1NP and CTX) changes were measured and compared between pre-treated and treatment naïve patients.
RESULTS: Ninety-nine patients (92 women and 7 men, median age 71 years [65, 76]) were enrolled from January 2021 to December 2023. Among them, 22 had no prior treatment before romosozumab, while 77 had previous therapy (including 23 with a history of prior teriparatide therapy), with a median duration of 6 years [4, 11] of cumulative antiresorptive treatment. Over 12 months, romosozumab led to BMD changes of 10.3% [7.5, 15.5] at the lumbar spine, 3.1% [1.1, 5.8] at the total hip and 3.1% [0.5, 5.3] at the femoral neck, indicating notable variability. Significantly lower BMD responses were observed in pre-treated patients, with the duration of prior antiresorptive therapy inversely associated with BMD increases at the lumbar spine and hip. Other predictors of BMD changes at the total hip included baseline T-scores at the hip, body mass index and baseline CTX level, while the BMD response at the lumbar spine was associated with the lumbar spine T-score at baseline, age and baseline CTX level.
CONCLUSIONS: Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip.

Bone loss below the level of neurological lesion is a well-known complication of spinal cord injury (SCI). To date, most research has focused on pharmaceutical intervention using antiresorptives to prevent bone loss during the acute phase of SCI; however, limited research has investigated treatments for established osteoporosis during chronic SCI. Romosozumab, a monoclonal antibody with both antiresorptive and anabolic effects, has demonstrated significant increases in BMD for women with established PMO. Therefore, the purpose of this study was to examine the efficacy of monthly treatment with romosozumab to improve DXA-derived areal BMD at the hip, and CT-derived BMC and strength at the hip and knee in women with chronic SCI and an inability to ambulate. Twelve female participants with chronic SCI were recruited to receive 1 yr of monthly subcutaneous injections of romosozumab (210 mg). DXA and CT scans were taken at baseline, and months 3, 6, and 12 to quantify bone mineral, and finite element (FE) analysis was used to predict bone strength. Longitudinal mixed effects models were employed to determine the impact of treatment on bone properties. After 12 mo of treatment, areal BMD at the lumbar spine and total hip were significantly increased with median changes of 10.2% (IQR: 8.3-15.2%, p<.001) and 4.2% (IQR: 3.4-7.7%, p = .009), respectively. Improvements at the hip were primarily due to increases in trabecular, not cortical, bone and effects were sufficient to significantly increase FE-predicted strength by 20.3% (IQR: 9.5-37.0%, p = .004). Treatment with romosozumab did not lead to any significant improvement in bone mineral at the distal femur or proximal tibia. These findings provide promising results for romosozumab treatment to improve bone mineral and reduce fracture risk at the hip, but not the knee, in women with chronic SCI.

In severe osteoporosis, the optimal approach for sequential treatment between denosumab and romosozumab is unclear. We utilised a novel overlapping strategy in three patients with very-high fracture risk despite long-term denosumab which led to greater bone density improvements than previously reported with standard approaches. Larger confirmatory prospective studies are needed.
OBJECTIVE: In patients with severe osteoporosis, the optimal approach for sequential treatment between denosumab and romosozumab has not been established. The ideal strategy would maximise gains in bone mineral density (BMD) with romosozumab and effectively mitigate the risk of rebound increased bone turnover when sequencing from denosumab. Limited studies exploring the sequence from denosumab to romosozumab report only modest-to-no improvement in BMD and inadequate suppression of rebound bone turnover.
METHODS: We describe three patients with severe osteoporosis and multiple fragility fractures despite long-term denosumab. A novel overlapping sequential treatment approach was utilised to maximise therapeutic benefit given these patients had a very high fracture risk. Romosozumab was commenced 3 months after the last denosumab dose. Instead of waiting until completion of romosozumab, denosumab was recommenced 6 months after commencing romosozumab in response to rising bone turnover markers.
RESULTS: Patients experienced a ~ 5-22% increase in lumbar spine BMD, and one patient had an 8% increase in total hip BMD after 12 months romosozumab. Serum bone turnover markers demonstrated an anabolic effect of romosozumab occurred despite overlapping treatment with denosumab. Recommencement of denosumab suppressed an increase in bone resorption in all cases. No new vertebral fractures occurred during this treatment.
CONCLUSIONS: A novel overlapping sequential treatment approach between denosumab and romosozumab produced greater improvements in lumbar spine and hip BMD than previously reported with standard approaches. Larger prospective controlled studies are needed to confirm these findings and establish the optimal use of romosozumab in patients pre-treated with denosumab to maximise BMD gains and minimise fracture risk.

Objective: The objective of the study is to highlight the role and safety of romosozumab in patients at high risk of fractures in primary care. Data Sources: A systemic database search of PubMed/MEDLINE, ClinicalTrials.gov, and Cochrane Library was conducted for articles with keywords romosozumab, osteoporosis, and safety between inception and July 2022. Study Selection and Data Extraction: Phase 3 trials in patients with osteoporosis were included. Data results from these trials were utilized for assessment. Data Synthesis: Romosozumab decreased vertebral fracture incidence by 73% at 12 months (P < 0.001) in osteoporotic postmenopausal women compared with placebo. In an active-controlled fracture study in postmenopausal women with osteoporosis at high risk of fracture, a 48% lower risk of new vertebral fracture was observed at 24 months in the romosozumab-alendronate group (P < 0.001) compared with alendronate group. In a study comparing romosozumab with teriparatide in postmenopausal women with osteoporosis at high risk of fracture, 2.6% of the mean percentage change from baseline in the total hip (TH) areal bone mineral density (BMD) was observed with romosozumab, while teriparatide led -0.6% of change (P < 0.0001). Romosozumab significantly increased the mean percentage change from baseline in the lumbar spine (LS) and total hip (TH) BMD than placebo in men with osteoporosis (LS, 12.1% vs 1.2%; TH, 2.5% vs -0.5%; P < 0.001). Serious cardiovascular events were observed in the romosozumab compared with alendronate (2.5% vs 1.9%; odds ratio [OR] = 1.31; 95% confidence interval [CI] = 0.85-2.00) in postmenopausal women, and placebo (4.9% vs 2.5%) in men with osteoporosis. Relevance to Patient Care and Clinical Practice: This review discusses the role of romosozumab in patients with high fracture risk and its safety in primary care. Conclusions: Primary care physicians should consider romosozumab for patients at high fracture risk who are intolerant or have not responded to other pharmacological treatment. Further studies are needed to clarify the safety of cardiovascular events.

OBJECTIVE: We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture healing of OVF in the patients with OVF via meta-analyses of randomized controlled trials (RCTs).
METHODS: Electronic databases, including PubMed, Embase, and Cochrane Library were searched for published RCTs till December 2022. The RCTs that recruited participants with osteoporosis at high-/very high-risk of fracture (a history of osteoporotic vertebral or hip fracture) or fresh OVF were included in this study. We assessed the risk of bias on every included RCTs, estimated relative risk (RR) for the incidence of new OVF and fracture healing of OVF, and overall certainty of evidence. Meta-analyses were performed by Cochrane review manager (RevMan) ver. 5.3. Cochrane risk of bias 2.0 and GRADEpro/GDT were applied for evaluating methodological quality and overall certainty of evidence, respectively.
RESULTS: Five hundred eighteen studies were screened, and finally 6 eligible RCTs were included in the analysis. In the patients with prevalent OVF, anabolic agents significantly reduced the incidence of new OVF (teriparatide and romosozumab vs. alendronate and risedronate [RR, 0.57; 95% confidence interval, 0.45-0.71; p < 0.00001; high-certainty of evidence]; teriparatide vs. risedronate [RR, 0.50; 95% confidence interval, 0.37-0.68; p < 0.0001; high-certainty of evidence]). However, there was no evidence of teriparatide compared to alendronate in fracture healing of OVF (RR, 1.23; 95% confidence interval, 0.95-1.60; p = 0.12; low-certainty of evidence).
CONCLUSIONS: In the patients with prevalent OVF, anabolic agents showed a significant superiority for preventing new OVF than BPs, with no significant evidence for promoting fracture healing of OVF. However, considering small number of RCTs in this study, additional studies with large-scale data are required to obtain more robust evidences.