Daniele Zuncheddu, Paola Buedo, Martin J. Stoddart, Laura B. Creemers, Sibylle Grad, Marcin Waligora
Background
Intervertebral disc degeneration (IDD) and osteoarthritis (OA) share many similarities in the molecular processes involved in the onset and progression of these musculoskeletal pathologies. Biological sex is a risk factor for both conditions. Sex bias in orthopedic preclinical research affects knowledge, reproducibility, and translational aspects of basic research. This article aims to provide a comprehensive overview of how donor sex is reported in IDD and OA preclinical research using human or animal samples and in vivo models.
Methods
We performed a cross-sectional study, searching original articles from journals with the highest impact factor in the field, to determine: (i) whether they report donor sex, and if so, whether they include this data in the analysis; and (ii) whether journals have requirements for sex reporting.
Results
Our research has four main outcomes. First, donor sex was reported in only 61.9% of the 284 cases examined. Second, among the studies where sex was reported (176), samples were predominantly from only male donors or animals (56%). Moreover, sex was rarely incorporated as a variable in outcome analysis (3.4% of cases). Finally, although 14 out of 23 journals stipulated sex reporting requirements, 37.7% of papers published in these journals failed to report donor sex.
Conclusions
Our results provide evidence for the under-reporting of sample donor sex in OA and IDD research, which may contribute to the poor translation to clinical efficacy and the replication crisis. Our findings could guide journal policies, institutional guidelines for preclinical research, and funder requirements.
{"title":"Biological Sex Is Under-Reported in Cartilage-Related Preclinical Research: A Cross-Sectional Analysis","authors":"Daniele Zuncheddu, Paola Buedo, Martin J. Stoddart, Laura B. Creemers, Sibylle Grad, Marcin Waligora","doi":"10.1002/jsp2.70104","DOIUrl":"https://doi.org/10.1002/jsp2.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intervertebral disc degeneration (IDD) and osteoarthritis (OA) share many similarities in the molecular processes involved in the onset and progression of these musculoskeletal pathologies. Biological sex is a risk factor for both conditions. Sex bias in orthopedic preclinical research affects knowledge, reproducibility, and translational aspects of basic research. This article aims to provide a comprehensive overview of how donor sex is reported in IDD and OA preclinical research using human or animal samples and in vivo models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a cross-sectional study, searching original articles from journals with the highest impact factor in the field, to determine: (i) whether they report donor sex, and if so, whether they include this data in the analysis; and (ii) whether journals have requirements for sex reporting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our research has four main outcomes. First, donor sex was reported in only 61.9% of the 284 cases examined. Second, among the studies where sex was reported (176), samples were predominantly from only male donors or animals (56%). Moreover, sex was rarely incorporated as a variable in outcome analysis (3.4% of cases). Finally, although 14 out of 23 journals stipulated sex reporting requirements, 37.7% of papers published in these journals failed to report donor sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results provide evidence for the under-reporting of sample donor sex in OA and IDD research, which may contribute to the poor translation to clinical efficacy and the replication crisis. Our findings could guide journal policies, institutional guidelines for preclinical research, and funder requirements.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James Melrose, Stone Sima, Neha Chopra, Ashish Diwan, Zi Gu
<div> <section> <h3> Background</h3> <p>One of the significant putative causes of low back pain (LBP) is degeneration of the intervertebral disc (IVD). Degenerated discs exhibit loss of proteoglycans, notably aggrecan, leading to mechanical dysfunction and aberrant nerve ingrowth. This pathological innervation results in the proliferation of nociceptive and mechanoreceptive neurons, significantly contributing to persistent pain. A critical therapeutic target is the dorsal root ganglion (DRG), which serves as a key neural hub for nociceptive signaling and neurogenic inflammation. Increased calcium influx through voltage-gated calcium channels within DRG neurons underpins heightened neuronal excitability, facilitating persistent pain transmission. Recent evidence highlights the promising role of bioactive peptides derived from reptilian and insect venoms as potent calcium channel blockers.</p> </section> <section> <h3> Methods</h3> <p>This conceptual review explores published evidence and mechanistic rationale on naturally occurring toxins and venoms as peptide calcium channel blockers for chronic LBP. We considered DRG targeted mechanisms and delivery approaches, including incorporation into biomimetic proteoglycans for localized, sustained intradiscal release, and their use along conventional nerve block procedures.</p> </section> <section> <h3> Results</h3> <p>Venom derived peptide families including ω-conotoxins from cone snail and Tx3-family spider peptides from Phoneutria nigriventer selectively block neuronal calcium channels (notably Ca<sub>v</sub>2.2), thereby reducing the release of neurotransmitters that propogate pain signals. Alongside these antinocicpetive effects, the targeted mechanism of action and directed modalities of these peptides offer a novel therapeutic approach with potential advantages over tradiitonal analgesics, which often present challenges related to tolerance and systemic side effects.</p> </section> <section> <h3> Conclusion</h3> <p>Naturally occurring bioactive peptide calcium channel blockers delivered either directly to the DRG or through a multifaceted therapeutic approach with biomimetic proteoglycans into the IVD or conventional nerve block procedures into the epidural space resents a promising future direction in managing chronic LBP. This approach warrants further pre-clinical and clinical evaluation to clarify clinical utility, potentially transforming pain management paradigms and significantly reducing healthcare burdens associated with chronic spinal disorders.</p> </section> </
{"title":"A Conceptual Review of Naturally Occurring Toxins and Venoms as Peptide Blockers to Combat Chronic Low Back Pain","authors":"James Melrose, Stone Sima, Neha Chopra, Ashish Diwan, Zi Gu","doi":"10.1002/jsp2.70107","DOIUrl":"https://doi.org/10.1002/jsp2.70107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>One of the significant putative causes of low back pain (LBP) is degeneration of the intervertebral disc (IVD). Degenerated discs exhibit loss of proteoglycans, notably aggrecan, leading to mechanical dysfunction and aberrant nerve ingrowth. This pathological innervation results in the proliferation of nociceptive and mechanoreceptive neurons, significantly contributing to persistent pain. A critical therapeutic target is the dorsal root ganglion (DRG), which serves as a key neural hub for nociceptive signaling and neurogenic inflammation. Increased calcium influx through voltage-gated calcium channels within DRG neurons underpins heightened neuronal excitability, facilitating persistent pain transmission. Recent evidence highlights the promising role of bioactive peptides derived from reptilian and insect venoms as potent calcium channel blockers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This conceptual review explores published evidence and mechanistic rationale on naturally occurring toxins and venoms as peptide calcium channel blockers for chronic LBP. We considered DRG targeted mechanisms and delivery approaches, including incorporation into biomimetic proteoglycans for localized, sustained intradiscal release, and their use along conventional nerve block procedures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Venom derived peptide families including ω-conotoxins from cone snail and Tx3-family spider peptides from Phoneutria nigriventer selectively block neuronal calcium channels (notably Ca<sub>v</sub>2.2), thereby reducing the release of neurotransmitters that propogate pain signals. Alongside these antinocicpetive effects, the targeted mechanism of action and directed modalities of these peptides offer a novel therapeutic approach with potential advantages over tradiitonal analgesics, which often present challenges related to tolerance and systemic side effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Naturally occurring bioactive peptide calcium channel blockers delivered either directly to the DRG or through a multifaceted therapeutic approach with biomimetic proteoglycans into the IVD or conventional nerve block procedures into the epidural space resents a promising future direction in managing chronic LBP. This approach warrants further pre-clinical and clinical evaluation to clarify clinical utility, potentially transforming pain management paradigms and significantly reducing healthcare burdens associated with chronic spinal disorders.</p>\u0000 </section>\u0000 </","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alaina L. Falck, Erick O. Buko, Kayla L. Chase, Diana Pendleton, Katie McDermott, Olivia Kim, Suhail P. Parvaze, Alexandra R. Armstrong, Susan A. Arnold, Elizabeth W. Bradley, Arin M. Ellingson, Christopher P. Ober, Aaron Rendahl, Casey P. Johnson
Background
Client-owned dogs presenting clinically with intervertebral disc disease (IVDD) are a potential comparative animal model to help advance the understanding of disc degeneration and its treatment. To utilize dog patients as a model, noninvasive imaging techniques are needed that can characterize subtle and progressive changes in disc health in longitudinal and treatment efficacy studies. The purpose of this study was to assess the sensitivity of quantitative MRI techniques in detecting disc degeneration in client-owned, nonchondrodystrophic-breed dogs.
Methods
Thoracolumbar vertebral columns from the donated bodies of 15 dogs without a history of IVDD were imaged at 3T MRI. Quantitative MRI maps (T2, T2*, T1ρ, adiabatic T1ρ, adiabatic T2ρ, and ADC) were acquired axially for 10 discs (T11-T12 to L7-S1), and median values were measured in the nucleus pulposus and annulus fibrosus. Four disc health measures (Pfirrmann grade, histology score, water content, and glycosaminoglycan content) were evaluated for each disc. The quantitative MRI and disc health measures were compared using linear models, and partial correlations (Rpartial) were calculated.
Results
Most dogs had both relatively healthy and degenerated discs as assessed by Pfirrmann grade and histology score. Quantitative MRI values in relatively healthy discs varied greatly between dogs but were similar across disc levels. In the nucleus pulposus, T2 relaxation times were moderately correlated with Pfirrmann grade (Rpartial = −0.62; p < 0.0001), histology score (Rpartial = −0.63; p < 0.0001), and water content (Rpartial = +0.45; p < 0.0001), and weakly correlated with glycosaminoglycan content (Rpartial = +0.31; p = 0.0047). T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ had similar relationships to the disc health measures in the nucleus pulposus. No notable relationships were observed with ADC or in the annulus fibrosus.
Conclusions
Quantitative T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques are similarly related to radiological and histological measures of disc health and water and glycosaminoglycan content in nonchondrodystrophic-breed dogs.
{"title":"Relationship Between Quantitative MRI and Radiological, Histological, and Biochemical Measures of Intervertebral Disc Health in Client-Owned, Nonchondrodystrophic-Breed Dogs","authors":"Alaina L. Falck, Erick O. Buko, Kayla L. Chase, Diana Pendleton, Katie McDermott, Olivia Kim, Suhail P. Parvaze, Alexandra R. Armstrong, Susan A. Arnold, Elizabeth W. Bradley, Arin M. Ellingson, Christopher P. Ober, Aaron Rendahl, Casey P. Johnson","doi":"10.1002/jsp2.70105","DOIUrl":"https://doi.org/10.1002/jsp2.70105","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Client-owned dogs presenting clinically with intervertebral disc disease (IVDD) are a potential comparative animal model to help advance the understanding of disc degeneration and its treatment. To utilize dog patients as a model, noninvasive imaging techniques are needed that can characterize subtle and progressive changes in disc health in longitudinal and treatment efficacy studies. The purpose of this study was to assess the sensitivity of quantitative MRI techniques in detecting disc degeneration in client-owned, nonchondrodystrophic-breed dogs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thoracolumbar vertebral columns from the donated bodies of 15 dogs without a history of IVDD were imaged at 3T MRI. Quantitative MRI maps (T2, T2*, T1ρ, adiabatic T1ρ, adiabatic T2ρ, and ADC) were acquired axially for 10 discs (T11-T12 to L7-S1), and median values were measured in the nucleus pulposus and annulus fibrosus. Four disc health measures (Pfirrmann grade, histology score, water content, and glycosaminoglycan content) were evaluated for each disc. The quantitative MRI and disc health measures were compared using linear models, and partial correlations (<i>R</i><sub>partial</sub>) were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most dogs had both relatively healthy and degenerated discs as assessed by Pfirrmann grade and histology score. Quantitative MRI values in relatively healthy discs varied greatly between dogs but were similar across disc levels. In the nucleus pulposus, T2 relaxation times were moderately correlated with Pfirrmann grade (<i>R</i><sub>partial</sub> = −0.62; <i>p</i> < 0.0001), histology score (<i>R</i><sub>partial</sub> = −0.63; <i>p</i> < 0.0001), and water content (<i>R</i><sub>partial</sub> = +0.45; <i>p</i> < 0.0001), and weakly correlated with glycosaminoglycan content (<i>R</i><sub>partial</sub> = +0.31; <i>p</i> = 0.0047). T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ had similar relationships to the disc health measures in the nucleus pulposus. No notable relationships were observed with ADC or in the annulus fibrosus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Quantitative T2, T2*, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques are similarly related to radiological and histological measures of disc health and water and glycosaminoglycan content in nonchondrodystrophic-breed dogs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carol M. Greco, Nathan E. Dodds, Amanda M. Acevedo, William Anderst, Kevin M. Bell, Jessa Darwin, Anthony Delitto, John M. Jakicic, Gina P. McKernan, Charity G. Patterson, Paul A. Pilkonis, Sara R. Piva, Michael J. Schneider, Nam V. Vo, Ajay D. Wasan, Lan Yu, Gwendolyn A. Sowa
Background
Chronic low back pain (cLBP) is complex, disabling, and costly to patients and to society. Patients' social circumstances, beliefs, and behaviors interact in a dynamic way with biomedical factors and have the potential to amplify or reduce suffering. It is important to assess the experience of pain via patient-reported outcomes (PROs). The University of Pittsburgh Mechanistic Research Center, entitled, “Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB3P),” is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB3P conducted a prospective, observational cohort study to identify phenotypes of over 1000 participants with cLBP. This article reports key information from the PROs and selected demographic variables obtained at the in-person LB3P study enrollment visit.
Methods
The LB3P study participants completed numerous PROs, including the minimum data set assessments of the NIH Research Task Force on back pain and the NIH HEAL Initiative's Common Data Elements. PROs were organized into five conceptual domains: (1) Pain Characteristics and Qualities, (2) Pain-related Psychosocial Factors, (3) General Psychosocial Factors, (4) General Health and Lifestyle Factors, and (5) Social Determinants of Health (SDoH). Patient Acceptance of Symptom Status, which consists of yes/no responses to 10 questions about whether the level of each of the 10 symptoms is satisfactory, was also assessed.
Results
PRO measures were collected from 1007 LB3P participants with cLBP. The means and standard deviations, or medians and interquartile ranges, and percentages for the PRO variables collected at the in-person enrollment visit are presented for the overall group and stratified by sex at birth (females and males) and by age (< 60 years old and ≥ 60 years old). For the participants overall, and across sex and age groups, pain intensity and interference were moderate on average. Neuropathic pain, assessed via PainDETECT, was present in 18% of the overall sample, and in 22.5% of those younger than 60. On average, fatigue, depressive and anxiety symptoms, memory and concentration, self-efficacy, and positive outlook were within normal limits, as indicated by PROMIS T-scores. However, PROMIS Physical function was below normal, with T-scores in the mild to moderate range of impairment. When participants were asked to rate the acceptability of their symptom status in 10 areas of function, the most frequently reported areas of dissatisfacti
{"title":"Patient-Reported Outcomes Among an Observational Cohort of Individuals With Chronic Low Back Pain","authors":"Carol M. Greco, Nathan E. Dodds, Amanda M. Acevedo, William Anderst, Kevin M. Bell, Jessa Darwin, Anthony Delitto, John M. Jakicic, Gina P. McKernan, Charity G. Patterson, Paul A. Pilkonis, Sara R. Piva, Michael J. Schneider, Nam V. Vo, Ajay D. Wasan, Lan Yu, Gwendolyn A. Sowa","doi":"10.1002/jsp2.70097","DOIUrl":"https://doi.org/10.1002/jsp2.70097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic low back pain (cLBP) is complex, disabling, and costly to patients and to society. Patients' social circumstances, beliefs, and behaviors interact in a dynamic way with biomedical factors and have the potential to amplify or reduce suffering. It is important to assess the experience of pain via patient-reported outcomes (PROs). The University of Pittsburgh Mechanistic Research Center, entitled, “<i>Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB</i><sup>3</sup><i>P),”</i> is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. LB<sup>3</sup>P conducted a prospective, observational cohort study to identify phenotypes of over 1000 participants with cLBP. This article reports key information from the PROs and selected demographic variables obtained at the in-person LB<sup>3</sup>P study enrollment visit.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The LB<sup>3</sup>P study participants completed numerous PROs, including the minimum data set assessments of the NIH Research Task Force on back pain and the NIH HEAL Initiative's Common Data Elements. PROs were organized into five conceptual domains: (1) Pain Characteristics and Qualities, (2) Pain-related Psychosocial Factors, (3) General Psychosocial Factors, (4) General Health and Lifestyle Factors, and (5) Social Determinants of Health (SDoH). Patient Acceptance of Symptom Status, which consists of yes/no responses to 10 questions about whether the level of each of the 10 symptoms is satisfactory, was also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PRO measures were collected from 1007 LB<sup>3</sup>P participants with cLBP. The means and standard deviations, or medians and interquartile ranges, and percentages for the PRO variables collected at the in-person enrollment visit are presented for the overall group and stratified by sex at birth (females and males) and by age (< 60 years old and ≥ 60 years old). For the participants overall, and across sex and age groups, pain intensity and interference were moderate on average. Neuropathic pain, assessed via PainDETECT, was present in 18% of the overall sample, and in 22.5% of those younger than 60. On average, fatigue, depressive and anxiety symptoms, memory and concentration, self-efficacy, and positive outlook were within normal limits, as indicated by PROMIS T-scores. However, PROMIS Physical function was below normal, with T-scores in the mild to moderate range of impairment. When participants were asked to rate the acceptability of their symptom status in 10 areas of function, the most frequently reported areas of dissatisfacti","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara R. Piva, Zakiy Alfikri, William Anderst, Kevin M. Bell, Cristiane Carlesso, Jessa Darwin, Anthony Delitto, Carol M. Greco, Marit E. Johnson, Gina P. McKernan, Rachel McLoughlin, Charity G. Patterson, Rachel E. Roos, Michael J. Schneider, Clair Smith, Gwendolyn A. Sowa, Nam V. Vo, Leming Zhou
<div> <section> <h3> Background</h3> <p>Despite the wide utilization of physical tests and pain assessments to evaluate individuals with chronic low back pain (cLBP), there is limited information about their feasibility in terms of test duration, the ability of individuals with cLBP to perform these tests, and associated adverse events. The literature also lacks reports on comprehensive characterization of physical tests to serve as a reference for clinicians and researchers. The objectives of the present work are to assess the feasibility of a comprehensive battery of physical tests and pain assessments germane to individuals with cLBP and characterize the tests' values in the context of a large cohort.</p> </section> <section> <h3> Methods</h3> <p>This cross-sectional analysis uses enrollment data from a large observational study conducted by the University of Pittsburgh Mechanistic Research Center—“Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB<sup>3</sup>P).” LB<sup>3</sup>P is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. Individuals with cLBP were screened by trained clinicians who assessed their safety to partake in up to 37 physical tests based on pre-existing medical conditions. Testers could elect not to administer tests based on their clinical judgment and participants could refuse to partake in tests. The reasons for not performing tests were recorded. The feasibility of the tests was assessed by the time to complete each test, percentages and reasons for tests not done, and adverse events related to test performance. Descriptive statistics for the physical tests were computed for the sample overall, and for the subgroups (male/female and age < 60/≥ 60) to serve as reference values for individuals with cLBP.</p> </section> <section> <h3> Results</h3> <p>The testing protocol took on average 130 min. In total, 8.9% of tests were not done. About one third of tests not done were screened out due to medical conditions identified during the safety screening, and two-thirds due to the tester's clinical judgment or participant refusal. Only four adverse events occurred, and they resolved without sequelae. The tests most often omitted were those requiring maximal and submaximal physical effort or could elevate blood pressure in those with hypertension, such as muscle strength testing of the hip, abdomen, and thigh, or hand immersion in cold water. From the 1007 participants enrolled in the study, those who did not complete one or more tests tended to be older, obese, less educated, and experienced more disability and back pain for a longer time. The descriptive statistics of th
{"title":"Feasibility of Physical Exam and Performance-Based Tests in Individuals With Chronic Low Back Pain: A Descriptive Study","authors":"Sara R. Piva, Zakiy Alfikri, William Anderst, Kevin M. Bell, Cristiane Carlesso, Jessa Darwin, Anthony Delitto, Carol M. Greco, Marit E. Johnson, Gina P. McKernan, Rachel McLoughlin, Charity G. Patterson, Rachel E. Roos, Michael J. Schneider, Clair Smith, Gwendolyn A. Sowa, Nam V. Vo, Leming Zhou","doi":"10.1002/jsp2.70096","DOIUrl":"https://doi.org/10.1002/jsp2.70096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite the wide utilization of physical tests and pain assessments to evaluate individuals with chronic low back pain (cLBP), there is limited information about their feasibility in terms of test duration, the ability of individuals with cLBP to perform these tests, and associated adverse events. The literature also lacks reports on comprehensive characterization of physical tests to serve as a reference for clinicians and researchers. The objectives of the present work are to assess the feasibility of a comprehensive battery of physical tests and pain assessments germane to individuals with cLBP and characterize the tests' values in the context of a large cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional analysis uses enrollment data from a large observational study conducted by the University of Pittsburgh Mechanistic Research Center—“Low Back Pain: Biological, Biomechanical, Behavioral Phenotypes (LB<sup>3</sup>P).” LB<sup>3</sup>P is part of the National Institutes of Health's Helping to End Addiction Long-term Initiative. Individuals with cLBP were screened by trained clinicians who assessed their safety to partake in up to 37 physical tests based on pre-existing medical conditions. Testers could elect not to administer tests based on their clinical judgment and participants could refuse to partake in tests. The reasons for not performing tests were recorded. The feasibility of the tests was assessed by the time to complete each test, percentages and reasons for tests not done, and adverse events related to test performance. Descriptive statistics for the physical tests were computed for the sample overall, and for the subgroups (male/female and age < 60/≥ 60) to serve as reference values for individuals with cLBP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The testing protocol took on average 130 min. In total, 8.9% of tests were not done. About one third of tests not done were screened out due to medical conditions identified during the safety screening, and two-thirds due to the tester's clinical judgment or participant refusal. Only four adverse events occurred, and they resolved without sequelae. The tests most often omitted were those requiring maximal and submaximal physical effort or could elevate blood pressure in those with hypertension, such as muscle strength testing of the hip, abdomen, and thigh, or hand immersion in cold water. From the 1007 participants enrolled in the study, those who did not complete one or more tests tended to be older, obese, less educated, and experienced more disability and back pain for a longer time. The descriptive statistics of th","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We read with interest the article by Xiaoqiang Wang et al. [1] titled “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells” published in JOR Spine on December 11, 2024. The study presents compelling findings on the role of puerarin in mitigating intervertebral disc degeneration (IDD). However, we would like to raise two critical points regarding the data analysis and interpretation that may affect the validity of the conclusions.
First, in Figure 1E, the intersection size of four different datasets is presented. However, the results appear counterintuitive: the intersection size increases as more datasets are included, while it decreases with fewer datasets. This observation contradicts mathematical principles, as the intersection of multiple datasets typically diminishes with the addition of more datasets due to increased variability and reduced common elements. We suggest that the authors revisit the methodology used to calculate these intersections and verify the data processing steps to ensure accuracy. Clarification on how the intersection sizes were derived would greatly enhance the reliability of this analysis.
Second, the authors did not explicitly state the log2FoldChange threshold used in their differential analysis. Based on Figure 2A, the absolute values appear to range between 0.2 and 0.3. Such a low threshold may result in an overly broad range of differentially expressed genes, potentially reducing the biological significance of the findings [2, 3]. We recommend that the authors justify their choice of threshold and consider applying a more stringent cutoff to improve the robustness of their results. Additionally, exploring the biological relevance of the identified genes through functional enrichment analysis could strengthen the study's conclusions [4].
We believe that addressing these issues would significantly enhance the clarity and impact of the study. We appreciate the authors' contributions to the field and hope that our comments will encourage further refinement of this important work. Thank you for considering our comments. We look forward to the authors' response and any potential follow-up studies.
{"title":"Comments on “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells”","authors":"Ji Jin, Miao Liu, Jiajie Guo, Hong Sun","doi":"10.1002/jsp2.70099","DOIUrl":"https://doi.org/10.1002/jsp2.70099","url":null,"abstract":"<p>We read with interest the article by Xiaoqiang Wang et al. [<span>1</span>] titled “Exploring the Therapeutic Potential of Puerarin on Intervertebral Disc Degeneration by Regulating Apoptosis of Nucleus Pulposus Cells” published in JOR Spine on December 11, 2024. The study presents compelling findings on the role of puerarin in mitigating intervertebral disc degeneration (IDD). However, we would like to raise two critical points regarding the data analysis and interpretation that may affect the validity of the conclusions.</p><p>First, in Figure 1E, the intersection size of four different datasets is presented. However, the results appear counterintuitive: the intersection size increases as more datasets are included, while it decreases with fewer datasets. This observation contradicts mathematical principles, as the intersection of multiple datasets typically diminishes with the addition of more datasets due to increased variability and reduced common elements. We suggest that the authors revisit the methodology used to calculate these intersections and verify the data processing steps to ensure accuracy. Clarification on how the intersection sizes were derived would greatly enhance the reliability of this analysis.</p><p>Second, the authors did not explicitly state the log2FoldChange threshold used in their differential analysis. Based on Figure 2A, the absolute values appear to range between 0.2 and 0.3. Such a low threshold may result in an overly broad range of differentially expressed genes, potentially reducing the biological significance of the findings [<span>2, 3</span>]. We recommend that the authors justify their choice of threshold and consider applying a more stringent cutoff to improve the robustness of their results. Additionally, exploring the biological relevance of the identified genes through functional enrichment analysis could strengthen the study's conclusions [<span>4</span>].</p><p>We believe that addressing these issues would significantly enhance the clarity and impact of the study. We appreciate the authors' contributions to the field and hope that our comments will encourage further refinement of this important work. Thank you for considering our comments. We look forward to the authors' response and any potential follow-up studies.</p>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Su, Longfei Jing, Dongmei Lv, Zhendong Huan, Wenqiang Xu
Background
Spinal cord injury (SCI) compromises the communication between the brain and spinal circuits involved in locomotion, resulting in severe motor dysfunction. However, currently available therapies have limited effectiveness in restoring motor function after SCI.
Objective
Recent research has highlighted the importance of the central pattern generator (CPG), a spinal circuitry responsible for generating coordinated patterns of leg motor activity in the absence of brain-derived inputs, in locomotor recovery. Therefore, a highly promising approach for restorative treatment after SCI involves reactivating the CPG network to harness its rhythmic activity-generating capabilities. Various forms of neuromodulation, such as pharmacological agents, electrical stimulation, and light-based regulatory strategies, have been utilized for this purpose.
Results
This review summarizes the organizational structure and functional characteristics of CPG networks, examines CPG alterations following SCI, and evaluates recent advances in neuromodulation strategies aimed at restoring motor function through CPG reactivation.
Conclusions
This review also highlights existing challenges and outlines prospective directions for future research in the field.
{"title":"Central Pattern Generators in Spinal Cord Injury: Mechanisms, Modulation, and Therapeutic Strategies for Motor Recovery","authors":"Hao Su, Longfei Jing, Dongmei Lv, Zhendong Huan, Wenqiang Xu","doi":"10.1002/jsp2.70100","DOIUrl":"https://doi.org/10.1002/jsp2.70100","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal cord injury (SCI) compromises the communication between the brain and spinal circuits involved in locomotion, resulting in severe motor dysfunction. However, currently available therapies have limited effectiveness in restoring motor function after SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Recent research has highlighted the importance of the central pattern generator (CPG), a spinal circuitry responsible for generating coordinated patterns of leg motor activity in the absence of brain-derived inputs, in locomotor recovery. Therefore, a highly promising approach for restorative treatment after SCI involves reactivating the CPG network to harness its rhythmic activity-generating capabilities. Various forms of neuromodulation, such as pharmacological agents, electrical stimulation, and light-based regulatory strategies, have been utilized for this purpose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This review summarizes the organizational structure and functional characteristics of CPG networks, examines CPG alterations following SCI, and evaluates recent advances in neuromodulation strategies aimed at restoring motor function through CPG reactivation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review also highlights existing challenges and outlines prospective directions for future research in the field.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144814956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, we aimed to create a rat model of incomplete spinal cord injury and to determine the relationship between muscle tone and gait characteristics during recovery from paralysis. This necessity stems from the need for animal models with motor function dynamics in rehabilitation development for spinal cord injury.
Methods
Thirty-eight-week-old male Sprague-Dawley rats were divided randomly into two groups: Sham and spinal cord injury groups. Three-dimensional gait analysis, Hoffman reflex, Basso-Beatie-Bresnahan score, muscle wet weight, and histological assessment were performed on postoperative days 3, 7, and 14, respectively.
Results
The incomplete spinal cord injury model showed paralysis recovery over time at postoperative day 14. At ground contact, the ankle plantar flexion angle was higher in the spinal cord injury group than in the Sham group on postoperative day 3; however, it reduced on postoperative day 14. Nevertheless, the ankle plantar flexion angle on the foot-off phase was significantly higher on postoperative days 3 and 14. The ankle abduction angle in the spinal cord injury group significantly increased over time and was higher than in the Sham group at all time points. Hoffmann reflex results showed that muscle tone was significantly higher in the spinal cord injury group on postoperative day 3 and increased over time. The model's gait was significantly affected by muscle tone changes.
Conclusion
The model provides a valuable tool for studying spastic gait and gait changes associated with improvement in paralysis.
{"title":"Gait Analysis During Paralysis Recovery in a Rat Incomplete Spinal Cord Injury Model","authors":"Misa Toyota, Shion Masuda, Daiki Nohara, Satoru Oba, Mayu Tomomitsu, Momoko Nagai-Tanima, Tomoki Aoyama","doi":"10.1002/jsp2.70102","DOIUrl":"https://doi.org/10.1002/jsp2.70102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In this study, we aimed to create a rat model of incomplete spinal cord injury and to determine the relationship between muscle tone and gait characteristics during recovery from paralysis. This necessity stems from the need for animal models with motor function dynamics in rehabilitation development for spinal cord injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-eight-week-old male Sprague-Dawley rats were divided randomly into two groups: Sham and spinal cord injury groups. Three-dimensional gait analysis, Hoffman reflex, Basso-Beatie-Bresnahan score, muscle wet weight, and histological assessment were performed on postoperative days 3, 7, and 14, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The incomplete spinal cord injury model showed paralysis recovery over time at postoperative day 14. At ground contact, the ankle plantar flexion angle was higher in the spinal cord injury group than in the Sham group on postoperative day 3; however, it reduced on postoperative day 14. Nevertheless, the ankle plantar flexion angle on the foot-off phase was significantly higher on postoperative days 3 and 14. The ankle abduction angle in the spinal cord injury group significantly increased over time and was higher than in the Sham group at all time points. Hoffmann reflex results showed that muscle tone was significantly higher in the spinal cord injury group on postoperative day 3 and increased over time. The model's gait was significantly affected by muscle tone changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The model provides a valuable tool for studying spastic gait and gait changes associated with improvement in paralysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jordin T. Marshall, Anthony D. Lutton, Mark W. Grinstaff, John W. Olesik, Benjamin A. Walter
Background
Daily cycles in tissue osmolarity within the intervertebral disc (IVD) are a biophysical signal that regulates cellular metabolism and arise from deformation of the charged and hydrated extracellular matrix (ECM). However, the magnitude of these osmotic cycles remains unclear due to spatial variations in ECM composition and fixed charge density (FCD) between the regions of the IVD and between the pericellular matrix (PCM) and surrounding ECM. This study aimed to (1) validate the use of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to assess intra-tissue sodium content and (2) apply this method to assess temporal and spatial changes in intra-tissue sodium content during a diurnal loading cycle.
Methods
The FCD of nucleus pulposus (NP) tissue was modified via equilibrium dialysis, and intra-tissue sodium was assessed via inductively coupled plasma-optical emission spectroscopy (ICP-OES) and LA-ICP-MS. In addition, tissue was stained with a cationic iodine-based contrast agent, and iodine was assessed via LA-ICP-MS. Diurnal changes in sodium were measured via LA-ICP-MS and ICP-OES in bovine caudal motion segments loaded under simulated physiologic loading for 40 (n = 4) or 48 (n = 4) hours, representing end-of-day and end-of-night deformations, respectively.
Results
Intra-tissue sodium content assessed via LA-ICP-MS strongly correlated (r ≥ 0.95) with ICP-OES sodium content, theoretical FCD values, and LA-ICP-MS iodine content in equilibrated tissue. Diurnal sodium results demonstrate that at the macroscale the NP region possessed a greater sodium content than the annulus fibrosus (AF) and experienced greater diurnal changes (“end-of-day-NP” sodium [0.52 ± 0.18 mEq Na/g wet wt], “end of night-NP” sodium [0.34 ± 0.13 mEq Na/g wet wt]) than the AF which did not experience a diurnal change. At the microscale, average PCM sodium normalized to adjacent ECM sodium at the end-of-day (2.3 ± 0.96) was greater than at the end-of-night (1.5 ± 0.38), indicating cells embedded within their specialized PCM likely experience elevated osmotic fluctuations.
{"title":"Spatial and Diurnal Variations in Sodium Content Within Intervertebral Disc Tissue","authors":"Jordin T. Marshall, Anthony D. Lutton, Mark W. Grinstaff, John W. Olesik, Benjamin A. Walter","doi":"10.1002/jsp2.70079","DOIUrl":"https://doi.org/10.1002/jsp2.70079","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Daily cycles in tissue osmolarity within the intervertebral disc (IVD) are a biophysical signal that regulates cellular metabolism and arise from deformation of the charged and hydrated extracellular matrix (ECM). However, the magnitude of these osmotic cycles remains unclear due to spatial variations in ECM composition and fixed charge density (FCD) between the regions of the IVD and between the pericellular matrix (PCM) and surrounding ECM. This study aimed to (1) validate the use of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to assess intra-tissue sodium content and (2) apply this method to assess temporal and spatial changes in intra-tissue sodium content during a diurnal loading cycle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The FCD of nucleus pulposus (NP) tissue was modified via equilibrium dialysis, and intra-tissue sodium was assessed via inductively coupled plasma-optical emission spectroscopy (ICP-OES) and LA-ICP-MS. In addition, tissue was stained with a cationic iodine-based contrast agent, and iodine was assessed via LA-ICP-MS. Diurnal changes in sodium were measured via LA-ICP-MS and ICP-OES in bovine caudal motion segments loaded under simulated physiologic loading for 40 (<i>n</i> = 4) or 48 (<i>n</i> = 4) hours, representing end-of-day and end-of-night deformations, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Intra-tissue sodium content assessed via LA-ICP-MS strongly correlated (<i>r</i> ≥ 0.95) with ICP-OES sodium content, theoretical FCD values, and LA-ICP-MS iodine content in equilibrated tissue. Diurnal sodium results demonstrate that at the macroscale the NP region possessed a greater sodium content than the annulus fibrosus (AF) and experienced greater diurnal changes (“end-of-day-NP” sodium [0.52 ± 0.18 mEq Na/g wet wt], “end of night-NP” sodium [0.34 ± 0.13 mEq Na/g wet wt]) than the AF which did not experience a diurnal change. At the microscale, average PCM sodium normalized to adjacent ECM sodium at the end-of-day (2.3 ± 0.96) was greater than at the end-of-night (1.5 ± 0.38), indicating cells embedded within their specialized PCM likely experience elevated osmotic fluctuations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
William R. Walsh, Rema A. Oliver, Matthew H. Pelletier, Tian Wang, Chris Christou, Emma R. Walsh, Jonathan M. Page, Chase T. Davis, Gregory M. Williams
Background
Calcium phosphate (CaP) biomaterials are widely used in surgical applications such as spinal fusion to substitute for or extend autogenous bone graft. Preclinical testing in standardized animal models is useful for evaluating the relative performance of materials differing in composition and structure, including a newer generation of submicron-structured CaP (sCaP) with surface features uniformly smaller than 1 μm. The purpose of this study was to compare three clinically available CaP-based materials and iliac crest autograft in the rabbit posterolateral fusion (PLF) model.
Methods
A novel sCaP with bovine collagen type I (sCaP/Col I) and two clinically established materials, sCaP with alkylene oxide copolymer (sCaP/AOC) and microstructured CaP with bovine collagen type I (mCaP/Col I), were evaluated in a skeletally mature, single-level, non-instrumented, bilateral rabbit PLF model. Iliac crest autograft served as a control. Endpoints included radiographic, mechanical, and histological evaluation at postoperative 6, 9, and 12 weeks.
Results
Fusion progressed with postoperative time with all grafts, and the CaP materials yielded fusion rates by micro-CT and manual palpation similar to those of the autograft control at each time point. When tested as autograft extenders, sCaP/Col I and sCaP/AOC demonstrated equivalent results for all endpoints. When hydrated with bone marrow aspirate and used as bone graft substitutes, sCaP/Col I supported earlier fusion than mCaP/Col I with an increased radiographic fusion rate at 9 weeks (p = 0.032) and increased bone tissue content by histomorphometry at 12 weeks (p = 0.006). New bone was observed to form with all materials, and no adverse local biological reactions were seen.
Conclusions
Differences in the composition and structure of clinically available CaP-based materials influenced the achievement of spinal fusion in a standardized rabbit PLF model. These results may help guide the selection and use of materials in clinical applications and the future development of biomaterials with improved performance.
{"title":"Comparative Performance of Calcium Phosphate Grafts and Iliac Crest Autograft in Posterolateral Spinal Fusion in Rabbits","authors":"William R. Walsh, Rema A. Oliver, Matthew H. Pelletier, Tian Wang, Chris Christou, Emma R. Walsh, Jonathan M. Page, Chase T. Davis, Gregory M. Williams","doi":"10.1002/jsp2.70101","DOIUrl":"https://doi.org/10.1002/jsp2.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Calcium phosphate (CaP) biomaterials are widely used in surgical applications such as spinal fusion to substitute for or extend autogenous bone graft. Preclinical testing in standardized animal models is useful for evaluating the relative performance of materials differing in composition and structure, including a newer generation of submicron-structured CaP (sCaP) with surface features uniformly smaller than 1 μm. The purpose of this study was to compare three clinically available CaP-based materials and iliac crest autograft in the rabbit posterolateral fusion (PLF) model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A novel sCaP with bovine collagen type I (sCaP/Col I) and two clinically established materials, sCaP with alkylene oxide copolymer (sCaP/AOC) and microstructured CaP with bovine collagen type I (mCaP/Col I), were evaluated in a skeletally mature, single-level, non-instrumented, bilateral rabbit PLF model. Iliac crest autograft served as a control. Endpoints included radiographic, mechanical, and histological evaluation at postoperative 6, 9, and 12 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fusion progressed with postoperative time with all grafts, and the CaP materials yielded fusion rates by micro-CT and manual palpation similar to those of the autograft control at each time point. When tested as autograft extenders, sCaP/Col I and sCaP/AOC demonstrated equivalent results for all endpoints. When hydrated with bone marrow aspirate and used as bone graft substitutes, sCaP/Col I supported earlier fusion than mCaP/Col I with an increased radiographic fusion rate at 9 weeks (<i>p</i> = 0.032) and increased bone tissue content by histomorphometry at 12 weeks (<i>p</i> = 0.006). New bone was observed to form with all materials, and no adverse local biological reactions were seen.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Differences in the composition and structure of clinically available CaP-based materials influenced the achievement of spinal fusion in a standardized rabbit PLF model. These results may help guide the selection and use of materials in clinical applications and the future development of biomaterials with improved performance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14876,"journal":{"name":"JOR Spine","volume":"8 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jsp2.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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