Post-craniopharyngioma surgery hypocalcemia due to denosumab use for osteoporosis: A case report.

RATIONALE: Denosumab, a fully humanized IgG monoclonal antibody, is commonly employed in the management of different types of osteoporosis. Up to now, hypocalcemia linked with denosumab has been predominantly reported in dialysis patients suffering from chronic kidney disease. Interestingly, there have been no reports of hypocalcemia following craniopharyngioma surgery with the use of denosumab. PATIENT CONCERNS: A 65-year-old male received a subcutaneous injection of denosumab (60 mg) as a treatment for osteoporosis following the resection of a craniopharyngioma. Remarkably, the patient developed hypocalcemia within 4 days post-injection. However, 6 months subsequent to the initial treatment, the patient underwent another subcutaneous injection of desmuzumab and once again experienced hypocalcemia. DIAGNOSES: Hypocalcemia. INTERVENTIONS: The hypocalcemia was successfully managed with intravenous calcium gluconate and oral calcium carbonate D3 tablets, leading to the alleviation of symptoms. OUTCOMES: Hypocalcemia following the use of denosumab after craniopharyngioma surgery is rare, and its occurrence may be associated with the primary disease and concomitant medications. LESSONS: It underscores the necessity for clinicians to perform a thorough evaluation of the patient's overall health status, complete all requisite testing, pay particular attention to those in high-risk categories, and ensure serum calcium levels are monitored, along with conducting other essential tests, prior to and following each administration of denosumab.

Effect of Denosumab or Alendronate on Vascular Calcification: Secondary Analysis of SALTIRE2 Randomized Controlled Trial.

BACKGROUND: Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment. METHODS AND RESULTS: In a double-blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F-sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24-month change in coronary calcium score, and 12-month changes in thoracic aorta calcium score, coronary and aortic 18F-sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [-64 to 148] Agatston units) and either denosumab (94 [0-212] Agatston units, P=0.24) or alendronic acid (34 [-62 to 134], P=0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22-512] Agatston units) and either denosumab (118 [11-340], P=0.75) or alendronic acid (116 [26-498] Agatston units, P=0.62). There were no differences in changes in coronary or aortic 18F-sodium fluoride activity between treatment groups. CONCLUSIONS: Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis. REGISTRATION: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Efficacy and safety of denosumab and teriparatide versus oral bisphosphonates to treat postmenopausal osteoporosis: a systematic review and meta-analysis.

Study Design: A systematic review and Meta-analysis. Objective: To compare the efficacy and safety of denosumab and teriparatide versus oral bisphosphonates to treat postmenopausal osteoporosis. Summary of Background Data: While bisphosphonates have historically been the cornerstone of pharmacological management for bone protection in patients, emerging evidence suggests that teriparatide and denosumab warrant further investigation as potential first-line treatments. The optimal choice among denosumab, teriparatide, and oral bisphosphonates for the treatment of postmenopausal osteoporosis remains a subject of ongoing debate and controversy within the scientific community. Methods: This systematic review adhered meticulously to the rigorous standards outlined by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines as well as the Cochrane Collaboration recommendations. Additionally, it employed the AMSTAR (Assessing the methodological quality of systematic reviews) criteria to ensure methodological robustness and enhance the credibility of the findings. A systematic electronic search was conducted across Web of Science, PubMed, and the Cochrane Library databases from their inception dates up to February 2024. Results: In this meta-analysis of studies, our findings suggest that compared to bisphosphonates, both teriparatide and denosumab demonstrated notable increases in percentage changes in lumbar spine bone mineral density (BMD) among postmenopausal osteoporosis patients. Furthermore, denosumab exhibited superiority over teriparatide and oral bisphosphonates in enhancing percentage changes in both femoral neck and total hip BMD, indicating its potential as a more efficacious option. Regarding safety outcomes, no significant differences were observed in the incidence of serious adverse events among patients treated with teriparatide, denosumab, and bisphosphonates. However, teriparatide showed superiority over oral bisphosphonates in terms of a lower risk of general adverse events, suggesting a favorable safety profile. Conclusion: In conclusion, our study suggests that teriparatide and denosumab demonstrate comparable or potentially superior efficacy and safety profiles compared to oral bisphosphonates for the treatment of postmenopausal osteoporosis. Systematic Review Registration: PROSPERO, identifier CRD42024508382.

Effect of denosumab, an anti-osteoporosis drug, on vascular calcification: A meta-analysis.

BACKGROUND: Denosumab is an effective drug for the treatment of osteoporosis. This meta-analysis was conducted to evaluate efficacy of denosumab on the treatment of vascular calcification (VC). METHODS: Databases including PubMed, EMbase, the Cochrane Library, CNKI, Wanfang database were searched from the inception to January 10th, 2024. Eligible studies comparing denosumab versus no denosumab treatment on VC were included. Data were analyzed using Review Manager Version 5.3. RESULTS: Five studies were included in this meta-analysis. Three were RCTs and 2 were non-randomized studies. As a whole, 961 patients were included in denosumab group and 890 patients were included in no denosumab group. The follow-up period was from 6 to 36 months. Compared with the no denosumab group, the denosumab group demonstrated a decrease on VC score or area in all enrolled patients (SMD -0.85, 95% CI -1.72-0.02, P = .05). In the subgroup of patients with non-CKD, there was no statistical difference between the denosumab and no denosumab group concerning the change of VC score (SMD -0.00, 95% CI -0.12-0.12, P = .98). In the subgroup of patients with CKD 3b-4, there was no significant difference between the denosumab and no denosumab group concerning the change of VC score (SMD 0.14, 95% CI -0.72-1.00, P = .75). In the subgroup of CKD patients undergoing dialysis, the denosumab group demonstrated a significant decrease on VC score or area compared with the no denosumab group (SMD -2.30, 95% CI -3.78-0.82, P = .002). CONCLUSION: Our meta-analysis revealed that denosumab did not show a very definite inhibitory effect on VC. However, denosumab showed the effective effect on inhibiting VC in CKD patients undergoing dialysis. More large RCTs are needed to verify these results.

The use of denosumab in osteoporosis - an update on efficacy and drug safety.

INTRODUCTION: Denosumab (Prolia) is a fully human monoclonal antibody against the receptor activator of the nuclear factor kappaB ligand. It is a potent antiresorptive agent that reduces osteoclastogenesis. AREAS COVERED: Denosumab has been shown to improve bone mineral density and reduce the incidence of new fractures in postmenopausal women and men. It is also used in the treatment of glucocorticoid-induced osteoporosis, as well as for the prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer. Initial safety concerns included infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures; however, further study and experience provide reassurance on these issues. Anecdotal reports have raised concerns about an increased risk of multiple vertebral fractures following discontinuation of denosumab. EXPERT OPINION: Although bisphosphonates are often selected as initial therapy for osteoporosis, denosumab may be an appropriate initial therapy in patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, as well as patients who are intolerant of, unresponsive to, or have contraindications to other therapies. Additional data is needed to address questions regarding treatment duration and discontinuation.

Denosumab combined with en bloc resection and arthrodesis for recurrent grade 3 giant cell tumor of bone in distal radius.

PURPOSE: This study aimed to analyse the clinical outcomes of preoperative adjuvant denosumab therapy (PADT) combined with resection and arthrodesis for recurrent grade 3 giant cell tumor of bone (GCTB) in the distal radius. METHODS: A retrospective study was conducted on twenty-three patients (8 males, 15 females) who were treated with the adjuvant denosumab combined with en bloc resection (EBR) and arthrodesis for biopsy confirmed recurrent Campanacci III giant cell tumor of bone in the distal radius between January 2015 and December 2022. All 23 patients were treated with wrist arthrodesis reconstruction using autogenous free iliac crest bone graft (ICBG), bridging plate and screws. The local control, metastasis and overall survival were evaluated during the follow-up period. Functional outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand (DASH) score, Musculoskeletal Tumor Society Score (MSTS-87 and MSTS-93), and grip strength in the follow-up period. Additionally, all surgical or denosumab-related complications that occurred were recorded in this study. RESULTS: Twenty-three patients were included in this retrospective study and no patients were lost in the follow-up period. The average patient age was 32.5 ± 10.2 years (range, 19-53 years) and the mean follow-up time was 35.5 ± 18.4 months (range, 13-72 months). The average tumor length was 71.7 ± 8.7 mm (range, 50 to 85 mm) and bone reconstruction length was 78.5 ± 8.5 mm (range, 60 to 90 mm). Four patients (17.4%) had secondary local recurrence after reoperation and two patients had (8.7%) multiple recurrences. One patient (4.3%) was deceased in the last follow-up due to multiple metastases. The estimated 5-year recurrence-free survival rate was 81.3% and 5-year metastasis-free survival rate was 95.7%. The mean union time was 8.5 ± 1.9 (6-12) months and the overall survivorship of the allograft was 82.7% (21/23) at an average 35 month follow-up. The average MSTS-87 and MSTS-93 scores were 27.8 ± 1.6 (range, from 23 to 30) and 91.5 ± 5.0 (range, from 76 to 100), and the average DASH score was 8.9 ± 3.2 (range, from 3 to 15), respectively. The average grip strength was 64.6 ± 15.7% (range, from 30 to 95%) of the uninvolved side. Eight patients (34.7%) had at least one complication in the follow-up time. Two autografts (8.7%) were removed due to local recurrence and bone nonunion, and the average autograft survival time was 32.8 ± 18.5 months (range, 12 to 72 months). CONCLUSIONS: Preoperative adjuvant denosumab therapy (PADT) combined with en bloc resection and arthrodesis is a promising method for the treatment of recurrent Campanacci III GCTB in distal radius with acceptable short-term local control and functional satisfaction. LEVEL OF EVIDENCE: level IV Therapeutic.

Do bisphosphonates and RANKL inhibitors alter the progression of coronary artery calcification? A systematic review.

OBJECTIVES: To determine whether bisphosphonates and NF-κB ligand (RANKL) inhibitors delay coronary artery calcification (CAC). DESIGN: A systematic review was conducted. DATA SOURCES: MEDLINE, EMBASE and CENTRAL. ELIGIBILITY CRITERIA: Longitudinal studies investigating CAC progression in adults (>18 years) taking either a bisphosphonate or denosumab compared with those who did not. DATA EXTRACTION AND SYNTHESIS: Study and participant characteristics, and primary outcome ( ∆ CAC from baseline to follow-up) were extracted. The Risk Of Bias In Non-Randomised Studies-of Interventions (ROBINS-I) and Risk-of-Bias Tool for Randomised Trials (RoB2) tools were used to assess the risk of bias for observational and randomised controlled trials (RCTs), respectively. Outcome measures were reported. RESULTS: Four observational studies and one RCT (n=377) were included. Three studies solely reported the effect of bisphosphonates on ∆ CAC; one study (n=56) demonstrated a statistically significant CAC reduction in the intervention group (-372 mm3/year) compared with control (+159 mm3/year) (p<0.01). One study (n=14) demonstrated a difference in ∆ CAC between intervention (+880 mm3/year) versus control (+2220 mm3/year), however, no p value comparing groups was reported. One study (n=115) found no statistically significant difference between intervention and control.One study (n=42) exclusively investigated the effect of RANKL on ∆ CAC; there was a statistically significant reduction in CAC at 6-month follow-up between intervention (-133±124 modified Agatston unit (AU)) and control (+188±72 modified AU), p=0.03.One study (n=150) compared both bisphosphonates and denosumab to control and found no statistically significant difference between either intervention group and control over 24 months. Meta-analysis was not performed due to limited, heterogeneous studies. CONCLUSIONS: There is insufficient evidence supporting the correlation between bisphosphonate or RANKL inhibitor use and CAC progression. Further research is warranted.

Efficacy and safety of teriparatide vs. bisphosphonates and denosumab vs. bisphosphonates in osteoporosis not previously treated with bisphosphonates: a systematic review and meta-analysis of randomized controlled trials.

The study found that in osteoporosis patients who had not previously received bisphosphonate treatment and were in a treatment cycle of over 12 months, both teriparatide and denosumab significantly increased bone mineral density compared to bisphosphonates. Additionally, teriparatide was also shown to significantly decrease the risk of fractures. OBJECTIVE: The systematic review and meta-analysis aimed to assess and compare the safety and efficacy of teriparatide vs. bisphosphonates and denosumab vs. bisphosphonates in patients with osteoporosis who had not previously received bisphosphonates. METHODS: We conducted a search of published literature from inception to May 31, 2023, including databases such as PubMed, Embase, Cochrane Library, CNKI, SinoMed, VIP, and WanFang. The study only included head-to-head randomized controlled trials (RCTs) that compared teriparatide and denosumab with bisphosphonates to treat patients with osteoporosis. Fixed-effect model and random-effect model were used due to clinical heterogeneity. Meta-analysis was performed via Stata 17.0. RESULTS: A total of 6680 patients were enrolled across 23 eligible trials. The results of the meta-analysis showed that teriparatide was superior to bisphosphonates in decreasing the risk of fracture (risk ratio (RR) = 0.61, 95% confidence interval (CI) (0.51, 0.74), P < 0.001). Denosumab showed no benefit compared to bisphosphonates in reducing the risk of fracture in treating osteoporosis (RR 0.99, 95% CI (0.62, 1.57), P = 0.96). Compared with bisphosphonates, teriparatide and denosumab could significantly improve femoral neck, total hip, and lumbar spine bone mineral density (BMD) (P < 0.05). Furthermore, teriparatide and denosumab did not increase the incidence of adverse events (teriparatide vs. bisphosphonates, RR 0.92, 95% CI (0.79, 1.08), P = 0.32; denosumab vs. bisphosphonates, RR 0.98, 95% CI (0.95, 1.02), P = 0.37). CONCLUSIONS: Teriparatide is superior to bisphosphonates in decreasing the risk of fracture in patients with osteoporosis. In addition, teriparatide and denosumab were more efficacious than bisphosphonates in increasing the percentage change in BMD at the femoral neck, total hip, and lumbar spine.

Bisphosphonate- and disumab-related gingival disorders: case analysis from the U.S. Food and Drug Administration Adverse Event Reporting System.

Prior research has indicated that bisphosphonates (BPs) can improve periodontal disease because of their anti-osteoporosis properties. In vitro studies have shown that BPs induce cytotoxicity, inhibit wound healing, and thus affect periodontal disease. Denosumab and BPs have alternative indications. BP and denosumab are not known to correlate with gingival disorders. We assessed such a relationship by applying Bayesian and nonproportional analyses to data in the US FDA Adverse Event Reporting System (FAERS) database. The study analyzed BPs and denosumab-reported incidents with preferred terms found in the narrow Standardized MedDRA Queries for gingival disorders. A total of 5863 reported cases of gingival disorders were associated with five BPs (alendronate, pamidronate, ibandronate, risedronate, and zoledronate) and denosumab. More than 15% of patients with gingival disorders related to BPs and denosumab other than denosumab were hospitalized over short- or long-term periods. Our findings indicated BPs and denosumab had significant reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) with respect to gingival disorders. Pamidronate had the highest association (ROR = 64.58, PRR = 57.99, IC = 5.71), while the weakest association was found with denosumab (ROR = 3.61, PRR = 3.60, IC = 1.77). Significant associations were found between the six drugs and gingival pain, gingival recession, gingivitis, periodontal disease, and periodontitis. In conclusion, our comprehensive overview of the correlations, clinical characteristics, and prognoses of BPs and denosumab-related gingival disorders suggests that these issues deserve continued surveillance and appropriate management.

MB09, a denosumab biosimilar candidate: Biosimilarity demonstration in a phase I study in healthy subjects.

This was a Phase I, randomized, double-blinded, three-arm, single-dose, parallel study aimed to demonstrate pharmacokinetic (PK) similarity between MB09 (a denosumab biosimilar candidate) and reference denosumab (XGEVA® from European Union [EU-reference] and United States [US-reference]) in a healthy male population. The primary PK endpoints included: Area under the serum concentration versus time curve from time 0 to the last quantifiable concentration timepoint (AUC0-last); and maximum observed serum concentration (Cmax). Secondary endpoints included: AUC from time 0 extrapolated to infinity (AUC0-∞), time to reach maximum observed concentration, clearance, terminal phase half-life, pharmacodynamic, safety, and immunogenicity assessments. A total of 255 subjects were randomized (1:1:1) to receive a subcutaneous 35 mg dose of MB09 or reference denosumab. Cmax was reached after denosumab administration, followed by a decline in the concentration with similar terminal phase half-live across treatment arms. Systemic exposure of MB09 (AUC0-last and Cmax) was equivalent to the reference denosumab, as the 90% confidence intervals around the geometric least square mean ratios laid within the predefined acceptance limits (80.00%, 125.00%) across all comparisons. Pharmacodynamic parameters, based on the percent of change from baseline in serum C-terminal telopeptide of Type 1 collagen levels, were similar across the three arms. The treatments were considered safe and generally well tolerated, with 92 treatment-emergent adverse events reported (most Grade 2 and 3) and similarly distributed. Immunogenicity was low and similarly distributed. These results provide strong evidence that supports the biosimilarity between MB09 and denosumab reference products.

Monoclonal Antibody Delivery Using 3D Printed Biobased Hollow µNe3dle Arrays for the Treatment of Osteoporosis.

Transdermal microneedles have demonstrated promising potential as an alternative to typical drug administration routes for the treatment of various diseases. As microneedles offer lower administration burden with enhanced patient adherence and reduced ecological footprint, there is a need for further exploitation of microneedle devices. One of the main objectives of this work was to initially develop an innovative biobased photocurable resin with high biobased carbon content comprising isobornyl acrylate (IBA) and pentaerythritol tetraacrylate blends (50:50 wt/wt). The optimization of the printing and curing process resulted in µNe3dle arrays with durable mechanical properties and piercing capacity. Another objective of the work was to employ the 3D printed hollow µNe3dles for the treatment of osteoporosis in vivo. The 3D printed µNe3dle arrays were used to administer denosumab (Dmab), a monoclonal antibody, to osteoporotic mice, and the serum concentrations of critical bone minerals were monitored for six months to assess recovery. It was found that the Dmab administered by the 3D printed µNe3dles showed fast in vitro rates and induced an enhanced therapeutic effect in restoring bone-related minerals compared to subcutaneous injections. The findings of this study introduce a novel green approach with a low ecological footprint for 3D printing of biobased µNe3dles, which can be tailored to improve clinical outcomes and patient compliance for chronic diseases.

Lymphocyte Infiltration Score and Spatial Characteristics Refined the Prognosis and Denosumab Treatment Responsiveness Indicators for Giant Cell Tumor of Bone.

PURPOSE: The prognostic value of lymphocyte infiltration score (LIS) and its nearest neighbor distance to tumor cells (NNDTC) in giant cell tumor of bone (GCTB) is currently not well established. This study aims to characterize LIS and NNDTC and examine their correlation with denosumab treatment responsiveness, clinicopathologic features, and patient prognosis. METHODS: Using multiplexed quantitative immunofluorescence, LIS was evaluated in 253 tumor specimens, whereas NNDTC was computed using HALO software. Subsequently, we analyzed the association of these parameters with patient outcomes (progression-free survival [PFS] and overall survival [OS]), clinicopathologic features, and denosumab treatment responsiveness. RESULTS: Low LIS was indicative of both poor PFS and OS (both P < .001). In addition, LIS was significantly associated with sex (P = .046), Enneking staging (P < .001), Ki-67 expression (P = .007), and denosumab treatment responsiveness (P = .005). Lower CD8+ (tumor interior [TI]) NNDTC, and CD3+ (TI) NNDTC were associated with worse PFS (P = .003 and .038, respectively), whereas lower CD8+ (TI) NNDTC was associated with worse OS (P = .001), but CD8+ (tumor infiltrating margin) NNDTC had the opposite effect (P = .002). Moreover, NNDTC showed a correlation with several clinicopathologic features. Importantly, LIS outperformed Enneking and Campanacci staging systems in predicting the clinical outcomes of GCTB. CONCLUSION: These findings suggest that LIS is a reliable predictive tool for clinically relevant outcomes and response to denosumab therapy in patients with GCTB. These parameters may prove to be useful in guiding prognostic risk stratification and therapeutic optimization for patients.

Effect of denosumab on the incidence of fractures and mortality in patients undergoing hemodialysis: A retrospective cohort study.

BACKGROUND: Patients undergoing hemodialysis are at an elevated risk of fractures; however, substantial evidence for osteoporosis treatment in this population is lacking. We explored the efficacy of denosumab, an anti-IgG2 antibody that targets the receptor activator of nuclear factor-kappa B ligand, in reducing fracture incidence and all-cause mortality in patients undergoing hemodialysis. METHODS: This retrospective cohort study-conducted from December 2013 to December 2022-evaluated the effects of denosumab on fracture incidence and all-cause mortality. Patients who initiated denosumab treatment during the study period were defined as the denosumab group, while those without a history of denosumab administration were defined as the non-denosumab group. Kaplan-Meier curves and log-rank tests were used to assess survival and fracture/mortality risks, respectively. Cox proportional hazards models were used to analyze both fractures and all-cause mortality. RESULTS: Among 214 patients undergoing hemodialysis, 52 (24.3%) received denosumab. The median age was 73.0 ± 11.5 years, with 92 (43.0%) females, and the median dialysis duration was 59 months (interquartile range, 6-126). During the study, thirty-seven non-denosumab-treated patients had fractures compared to eight in the denosumab group. No significant differences were observed in the unadjusted model (HR, 0.53; 95% confidence interval (CI), 0.24-1.14). Adjusting for competing mortality and clinical factors, the HR remained at 0.64 (95% CI, 0.27-1.51). Regarding all-cause mortality, we found a statistically significant difference in the unadjusted model (HR, 0.61 [95% CI, 0.38-0.98]). A significant reduction in mortality was observed in the adjusted model (HR, 0.46 [95% CI, 0.26-0.80]). Notably, the denosumab group showed a significant decrease in mortality, particularly in cardiovascular disease-related cases (HR, 0.33 [95% CI, 0.14-0.78]). CONCLUSIONS: Denosumab may reduce all-cause mortality in patients undergoing hemodialysis, particularly in those with cardiovascular complications. This finding offers a promising direction for osteoporosis treatment in patients undergoing hemodialysis.

Combined preoperative denosumab and adjuvant microwave ablation for high-risk giant cell tumor of bone: a retrospective study in a single center.

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive neoplasm with a high propensity for recurrence following intralesional curettage. The introduction of denosumab, a RANKL inhibitor, has shown potential in facilitating joint-sparing surgery. However, concerns exist regarding its impact on local recurrence rates. This study aimed to evaluate the efficacy and safety of combined preoperative denosumab with adjuvant microwave ablation (MWA) for the treatment of high-risk GCTB. METHODS: We conducted a retrospective review of 19 patients with high-risk GCTB who underwent preoperative denosumab treatment followed by curettage and adjuvant MWA. The primary outcome measure was the local recurrence rate, with secondary outcomes including functional status assessed by the Musculoskeletal Tumor Society (MSTS) score and safety profile of the treatment. RESULTS: In this retrospective analysis, we evaluated the outcomes of 19 patients with high-risk GCTB treated with preoperative denosumab and adjuvant MWA. The median follow-up duration was 33.1 months, 3 patients (15.8%) experienced local recurrence at a median of 21.6 months postoperatively and the local recurrence-free survival was 81.2% at two years. Notably, no patient developed lung metastasis, and all recurrences were successfully managed with repeat curettage and MWA, with a mean MSTS score of 27.3. No patient required joint replacement due to tumor recurrence, resulting in a 100% joint preservation rate. CONCLUSION: The combination of preoperative denosumab and adjuvant MWA is a feasible and effective strategy for the management of high-risk GCTB, providing effective local control with preserved joint function. This approach may offer a surgical alternative for young patients where joint preservation is paramount.

Impact of Teriparatide and Denosumab on Clinical and Radiographic Outcomes in Osteoporotic Vertebral Compression Fractures.

Background and Objectives: Osteoporotic vertebral compression fractures (OVCFs) are prevalent among the elderly, often leading to significant pain, morbidity, and mortality. Effective management of underlying osteoporosis is essential to prevent subsequent fractures. This study aimed to compare the clinical and radiographic outcomes of teriparatide and denosumab treatments in patients with OVCFs to determine their relative effectiveness in improving patient outcomes. Materials and Methods: This retrospective study included 78 patients diagnosed with an acute thoracolumbar OVCF who received either teriparatide (35 patients) or denosumab (43 patients) within three months of a fracture. Clinical outcomes were assessed using the visual analog scale (VAS) for back pain, Oswestry disability index (ODI), and EQ-5D quality of life scores at baseline, 6 months, and 12 months. Bone mineral density (BMD) and radiographic outcomes were evaluated initially and at 12 months post-treatment. Results: Both treatment groups demonstrated significant improvements in VAS, ODI, and EQ-5D scores over 12 months. No significant differences were observed between the teriparatide and denosumab groups in terms of clinical outcomes or radiographic measurements at any time point. Fracture union and BMD improvements were similarly observed in both groups. The teriparatide group had a lower baseline BMD, but this did not affect the overall outcomes. Conclusions: Both teriparatide and denosumab are effective in improving clinical and radiographic outcomes in patients with OVCFs. Despite concerns about denosumab's potential to hinder fracture healing, our study found no significant differences between the two treatments. These findings support the use of denosumab for early treatment of OVCFs to prevent subsequent fractures without compromising fracture healing. Further prospective studies are needed to confirm these results.

Romosozumab followed by denosumab versus denosumab only: a post hoc analysis of FRAME and FRAME extension.

Osteoanabolic-first treatment sequences are superior to oral bisphosphonates for fracture reduction and bone mineral density (BMD) gain. However, data comparing osteoanabolic medications, with the more potent antiresorptive, denosumab (DMAb), are limited. We analyzed FRAME and FRAME Extension data to assess BMD and fracture incidence in patients treated with romosozumab (Romo) followed by DMAb (Romo/DMAb) versus DMAb (DMAb/DMAb) for 24 months. In FRAME, women aged ≥55 years (total hip [TH] or femoral neck [FN] T-score: -2.5 to -3.5) were randomized to Romo or placebo for 12 months followed by DMAb for 12 months. In FRAME Extension, both cohorts received DMAb for another 12 months. This post hoc analysis compared BMD change and fracture incidence in patients on Romo/DMAb (months 0-24) versus DMAb/DMAb (months 12-36). Patient characteristics were balanced by propensity score weighting (PSW) and sensitivity analyses were conducted using PSW with multiple imputation (PSW-MI) and propensity score matching (PSM). Unmeasured confounding was addressed using E-values. After PSW, over 24 months, compared with DMAb/DMAb, treatment with Romo/DMAb produced significantly greater BMD increases at the lumbar spine [LS], TH, and FN (mean differences: 9.3%, 4.4%, and 4.1%, respectively; all p<0.001). At month 24, in women with a baseline T-score of -3.0, the probability of achieving a T-score > -2.5 was higher with Romo/DMAb versus DMAb/DMAb (LS: 92% versus 47%; TH: 50% versus 5%). In the Romo/DMAb versus DMAb/DMAb cohorts, new vertebral fractures were significantly reduced (0.62% versus 1.26% [odds ratio = 0.45; p=0.003]) and rates of clinical, nonvertebral, and hip fractures were lower (differences not significant). Similar BMD and fracture outcomes were observed with PSW-MI and PSM sensitivity analyses. The sequence of Romo/DMAb resulted in greater BMD gains and higher probability of achieving T-scores > -2.5, significantly reduced new vertebral fracture incidence, and numerically lowered the incidence (not significant) of clinical, nonvertebral, and hip fractures versus DMAb only through 24 months.

In patients with very high fracture risk, a treatment sequence with a bone-forming agent, followed by a bisphosphonate (one type of antiresorptive that reduces bone loss) is more effective in increasing bone mineral density (BMD) and reducing fracture risk compared to treatment with bisphosphonates alone. Here, we utilized patient data from the FRAME and FRAME Extension clinical trials to compare changes in BMD and fracture incidence in postmenopausal women with osteoporosis treated with the bone-forming agent, romosozumab (Romo), for 12 months followed by the most potent antiresorptive, denosumab (DMAb), for 12 months (Romo/DMAb) versus patients treated with DMAb alone for 24 months. Propensity score weighting was used to balance the patient characteristics between the two groups. We found that BMD gains were significantly higher in patients treated with the Romo/DMAb sequence versus DMAb alone; these patients also had a higher probability of achieving a T-score above the osteoporosis range (>­2.5). In addition, new vertebral fractures were significantly lower and rates of clinical, nonvertebral, and hip fractures trended lower in patients treated with the Romo/DMAb sequence versus DMAb alone. Thus, a 24-months treatment sequence of Romo/DMAb compared with DMAb alone, resulted in higher BMD gains and lower fracture risk.

The Role of Denosumab Treatment in Recurrent Giant Cell Bone Tumor of the Orbit.

Giant cell tumor of the bone (GCTB) is a rare primary bone neoplasm, representing about 5% of all primary bone tumors. Most GCTBs are found in the epiphysis of long bones, with only 2% of GCTBs involving the skull. In recent years, the receptor activator of nuclear factor Kappa ligand monoclonal antibody denosumab has been demonstrated as a promising therapeutic option for GCTB; however, this is an evolving field. We present a case of a 57-year-old female with a rare GCTB in the right orbit and sinuses, originally thought to be an aneurysmal bone cyst. Her symptoms included proptosis, intermittent blurry vision, sinus congestion, and frontal headaches. After excision, the tumor recurred within 18 months. Upon repeat excision, a diagnosis of GCTB was made. The patient started denosumab therapy and had no tumor growth over the ensuing 2 years, with stability of symptoms and clinical signs on follow-up.