**Background:** Osteoporotic vertebral compression fracture (OVCF) is a major health problem in the elderly, with approximately 20% of adults over 70 years and 16% of postmenopausal women affected. Percutaneous vertebroplasty is the most common surgical treatment due to rapid pain relief and vertebral height restoration, but refracture after surgery remains a concern. Low bone mineral density (BMD) is the most important risk factor for refracture. Teriparatide, a recombinant human parathyroid hormone, is an anabolic agent that improves BMD and bone strength, but its high cost, daily injection requirement, and bone mass loss after discontinuation limit its use. Bisphosphonates like alendronate are anti-resorptive agents that can maintain BMD gains after teriparatide cessation. This study investigated whether a short sequential regimen of teriparatide (6 months) followed by alendronate (6 months) could reduce refracture rates and improve BMD compared to alendronate alone in postmenopausal women after percutaneous vertebroplasty.
**Methods:** This prospective, two-center study was conducted from January 2018 to January 2020 at two hospitals in Guangdong Province, China. A total of 215 female patients aged 55–80 years with fresh OVCF (Genant type I–II) who had undergone percutaneous vertebroplasty within 30 days and had T-scores < -2.5 were screened. Exclusion criteria included secondary osteoporosis, malignant disease, prior bisphosphonate or parathyroid hormone use, kidney disease, gastrointestinal disorders, and medications affecting bone metabolism. After exclusions (24 attending other clinics, 29 declining participation), 162 patients were enrolled and assigned by patient choice to either the sequential teriparatide+alendronate group (TPTD+ALN, n=80) or alendronate-alone group (ALN, n=82). During follow-up, 57 patients withdrew (29 switched therapies, 16 non-compliant, 12 lost to follow-up), leaving 105 completers (46 TPTD+ALN, 59 ALN). The TPTD+ALN group received daily subcutaneous teriparatide 20 μg for 6 months followed by oral alendronate 70 mg weekly for 6 months; the ALN group received alendronate 70 mg weekly for 12 months. Both groups received calcium 1200 mg/day and vitamin D 800 IU/day. BMD at lumbar spine, femoral neck, and total hip was measured by dual-energy X-ray absorptiometry at baseline and at 3, 6, 9, and 12 months. Serum PINP (bone formation marker) and CTX (bone resorption marker) were measured at the same intervals. Refractures were confirmed by X-ray and MRI. Statistical analyses used independent t-tests, Mann-Whitney U tests, paired t-tests, and Fisher's exact test as appropriate.
**Key Results:** Baseline characteristics were similar between groups (mean age 67.5±4.9 vs. 67.4±4.6 years; lumbar BMD 0.569±0.069 vs. 0.567±0.064 g/cm²; PINP 41.76±5.39 vs. 42.94±7.32 ng/ml; CTX 0.468±0.10 vs. 0.453±0.118 ng/ml; all p>0.05). The total refracture rate was significantly lower in the TPTD+ALN group (6.5%, 3/46) compared to the ALN group (23.7%, 14/59; p=0.015). Vertebral refracture occurred in 1 patient (2.2%) in the TPTD+ALN group versus 8 patients (13.6%) in the ALN group (p=0.038). Non-vertebral fractures occurred in 2 (4.3%) vs. 6 (10.2%) patients (p=0.231). At 12 months, lumbar spine BMD was significantly higher in the TPTD+ALN group (0.65±0.10 g/cm²) compared to the ALN group (0.57±0.07 g/cm²; p<0.001). Within the TPTD+ALN group, lumbar BMD at 12 months was significantly increased from baseline (0.569±0.069 vs. 0.65±0.10 g/cm²; p<0.001). Femoral neck BMD at 12 months showed no significant between-group difference, but both groups had significant within-group increases from baseline (TPTD+ALN: p<0.001; ALN: p<0.01). Total hip BMD showed only modest within-group changes (p<0.05). PINP and CTX levels were significantly higher in the TPTD+ALN group at all post-baseline time points (p<0.001). In the TPTD+ALN group, PINP at 12 months remained significantly above baseline (41.76±5.40 vs. 74.64±13.68 ng/ml; p<0.001), while CTX at 12 months fell below baseline (0.47±0.10 vs. 0.37±0.14 ng/ml; p<0.01). In the ALN group, both PINP and CTX at 12 months were significantly reduced from baseline (p<0.001). VAS pain scores improved significantly in both groups from baseline to 12 months (p<0.05), with no between-group difference.
**Clinical Implications:** This study demonstrates that a short 6-month course of teriparatide followed by 6 months of alendronate is more effective than alendronate alone for increasing lumbar spine BMD and reducing vertebral refracture risk in postmenopausal women after percutaneous vertebroplasty. The sequential approach leverages the anabolic window of teriparatide (peak bone formation at ~6 months) and then consolidates gains with alendronate's anti-resorptive effect, resulting in sustained net bone formation (elevated PINP with suppressed CTX at 12 months). This strategy may offer a cost-effective alternative to longer teriparatide courses by limiting treatment duration while preserving BMD benefits. Limitations include the non-randomized assignment, small sample size, short follow-up (12 months), and high dropout rate (35%). Larger randomized trials with longer follow-up are needed to confirm these findings and assess long-term fracture outcomes.