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Spine Journal - 2026-03-03 - Journal Article

The association of operative versus nonoperative treatment for lumbar spondylolisthesis and stenosis with future metabolic conditions and allostatic burden: an emulated target trial.

Ibrahim MT, Kuttner N, Schoenfeld RJ, Alvarez P, Kavuri V, Singh VK, Schoenfeld AJ, Yu E

retrospective cohortLOE IIIn = 2,521,827 (329,314 surgical, 2,192,513 nonoperative)3 years for metabolic outcomes; 2 years for opioid outcomes.

Topics

spine
PMID: 41786223DOI: 10.1016/j.spinee.2026.03.003View on PubMed ->

Key Takeaway

Surgical treatment for lumbar spondylolisthesis and stenosis within 6 months of diagnosis reduced 3-year metabolic burden risk by 6–7% (RR 0.94) compared to nonoperative care, but surgery was associated with 19% higher risk of active opioid prescription at 3 years.

Summary Depth

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Summary

This emulated target trial used EPIC COSMOS data and clone analysis with inverse probability weighting to compare surgical versus nonoperative treatment on metabolic burden, frailty, chronic pain, and allostatic load. Surgery within 12 months reduced 1- and 3-year metabolic burden risk (RR 0.98) and frailty (RR 0.98–0.99), with maximal benefit when surgery occurred within 6 months (3-year RR 0.94). However, the surgical cohort carried a significantly higher risk of active opioid prescription at both 1 year (RR 1.04) and 3 years (RR 1.19), and allostatic load differences were negligible.

Key Limitation

The absolute risk reductions are clinically marginal (RR 0.93–0.99), and the extremely narrow confidence intervals driven by the massive sample size likely reflect statistical rather than clinically meaningful differences, making direct translation to individual surgical decision-making unreliable.

Original Abstract

BACKGROUND CONTEXT

Lumbar spinal stenosis adversely impacts mobility and function. Persistent lack of exercise and ambulatory capacity may contribute to the development of metabolic conditions.

PURPOSE

To determine the effect of surgical intervention, as compared to non-operative treatment, on the development of metabolic conditions, chronic pain, frailty, and allostatic load (AL).

STUDY DESIGN

Retrospective emulation target trial.

PATIENT SAMPLE

A total of 2,521,827 patients were included, of which 329,314 (13.1%) underwent surgery.

OUTCOME MEASURES

Development of metabolic conditions, chronic pain, frailty, and allostatic load (AL).

METHODS

Data was sourced from EPIC COSMOS. We conducted a clone analysis using inverse probability censoring weights and inverse probability of treatment weights that accounted for confounders. Risk ratios (RR) were calculated at 1- and 3-years post-index diagnosis for post-operative metabolic burden and frailty, and at 1 and 2 years for active opioid prescription, using weighted pooled logistic regression. Generalized Estimating Equation was used to determine the mean difference in AL at 1 and 3 years.

RESULTS

Surgery within 12 months of index diagnosis demonstrated a significantly lower risk of metabolic burden (1-year RR [95% confidence interval (CI)]: 0.98 [0.98 to 0.98]; 3-year: 0.98 [0.98 to 0.98]) and frailty (1-year: 0.98 [0.98 to 0.99]; 3-year: 0.99 [0.98 to 0.99]). The risk of metabolic burden was lowest if surgery occurred within 6 months (1-year RR [95% CI]: 0.93 [0.93 to 0.94]; 3-year RR [95% CI]: 0.94 [0.94 to 0.95]). No significant difference in AL was noted at 1-year, and the difference was negligible at 3-years. The surgery cohort had a higher risk of active opioid prescription at 1-year (RR [95% CI]: 1.04 [1.04 to 1.04]) and 3-year (RR [95% CI]: 1.19 [1.17 to 1.20]) follow-up.

CONCLUSIONS

We found that surgical intervention was associated with greater reductions in metabolic burden and frailty up to 3 years following the procedure. We also found evidence of a time-dependent effect such that maximal benefit was appreciated when surgery was performed within 6-months of presentation.