Background/Objectives: Abaloparatide is an osteoanabolic therapy used in patients at high risk of fracture; however, the breadth of evidence across routes, comparators, and sequential strategies has not yet been comprehensively summarized. This study aimed to evaluate the efficacy and safety of abaloparatide for reducing fractures and improving bone mineral density (BMD) in adults with osteoporosis. Methods: Following PRISMA 2020, we searched PubMed, Embase, CENTRAL, and Web of Science (2016–2024) for randomized controlled trials and comparative real-world studies. Additional meta-analyses and network meta-analyses were included as contextual evidence but not pooled to avoid double-counting. Primary outcomes were vertebral, non-vertebral, and hip fractures; secondary outcomes included percentage change in BMD and safety endpoints. Random-effects models were used; heterogeneity, influence analyses, and prediction intervals were examined. Risk of bias was assessed using RoB 2 and AMSTAR 2. Results: Nine quantitative evidence sources met the criteria. Abaloparatide reduced vertebral fractures (RR 0.13–0.21) and showed moderate reductions in non-vertebral fractures. Lumbar spine BMD increased substantially, while hip and femoral neck gains were smaller and heterogeneous. Hypercalcemia risk was consistently lower compared to teriparatide. Transdermal delivery was less effective, and sequential abaloparatide → antiresorptive therapy further reduced fractures. Serious adverse events were not increased. Conclusions: Abaloparatide provides strong vertebral protection, significant BMD improvement, and shows a favorable calcemic profile, with moderate certainty for non-vertebral effects. Evidence in men and long-term safety remains limited.

Background: A previous short-term retrospective analysis from our center suggested early improvement in pain, function, and sleep outcomes after fixed-dose tramadol/paracetamol therapy in patients with early-stage symptomatic knee osteoarthritis (KOA). However, the durability of these outcomes beyond the initial treatment phase remains insufficiently described in routine clinical practice. Objective: To describe short- and mid-term patient-reported outcomes and safety during extended follow-up in adults with symptomatic KOA treated with fixed-dose tramadol/paracetamol in routine outpatient care. Methods: This single-center retrospective observational extension study analyzed a fixed cohort of 30 adults with symptomatic knee osteoarthritis and Kellgren–Lawrence grade I–II treated with fixed-dose tramadol/paracetamol in routine outpatient care. Patients were evaluated at baseline (T0), 15 days (D15), 3 months (M3), and 6 months (M6), where evaluable follow-up data were available. The primary outcome was change in pain intensity measured by the Numeric Rating Scale (NRS). Secondary outcomes included WOMAC total and subscale scores, Pittsburgh Sleep Quality Index (PSQI) score, adverse events, and treatment discontinuation. Results: Patients had a mean age of 64.8 ± 9.6 years and a mean BMI of 27.3 ± 5.0 kg/m². NRS pain improved from a median of 6.0 (5.0–7.0) at baseline to 4.0 (2.0–5.3) at D15 and 3.0 (2.0–5.0) at both M3 and M6. WOMAC total score improved from 47.8 ± 12.8 at baseline to 35.6 ± 13.8 at D15, 33.8 ± 13.6 at M3, and 33.9 ± 13.5 at M6. Sleep score improved from 9.5 (7.0–15.0) at baseline to 7.0 (5.0–9.0) at D15 and remained improved at M3 and M6. Mild adverse events were reported in 10.0% of patients, and discontinuation occurred in 6.7%. Conclusions: In this small, uncontrolled, single-center retrospective cohort of adults with early-stage symptomatic KOA, fixed-dose tramadol/paracetamol was associated with early improvement in pain, WOMAC outcomes, and sleep, with group-level benefits remaining evident through 6 months. These findings should be considered exploratory and hypothesis-generating rather than comparative evidence of effectiveness. Larger controlled studies are needed to confirm durability, comparative benefit, and long-term safety.