New findings in musculoskeletal basic science are presented in the recent JBJS Guest Editorial What’s New in Musculoskeletal Basic Science. Here, we highlight the 5 most noteworthy studies, as selected by author Zbigniew Gugala, MD, PhD.
Neuroimmune Modulation of Tissue Healing
Researchers found that tissue healing involves complex neuroimmune interactions mediated by calcitonin gene-related peptide (CGRP). Decreased CGRP expression in sensory neurons was observed in mice without the NaV1.8 channels and in mice with diabetic neuropathy. The mice demonstrated impaired tissue healing that was mitigated with local exogenous CGRP delivery. “Harnessing neuro-immune interactions has potential to treat non-healing tissues in which dysregulated neuro-immune interactions impair tissue healing,” concluded the study authors1.
Regulation of Bone Homeostasis
A mechanistic study identified a potent brain-derived osteoanabolic hormone, cellular communication network factor 3 (CCN3), that is released in the early postpartum period throughout lactation, during which increased calcium demand and decreased estrogen contribute to bone loss. CCN3 increased osteogenic differentiation and matrix mineralization in human stem cells, regardless of cell donor age and sex. Locally delivered CCN3 accelerated healing after femoral osteotomy in female and male mice2.
Bone and Its Blood Supply
Vascularization in murine calvarial defect healing was longitudinally observed in a dynamic imaging study using intravital multiphoton microscopy. Unlike in femoral fracture-healing, angiogenesis was found to be uncoupled from osteogenesis in calvarial healing, and angiogenesis and hypoxia-related genes were only slightly expressed3. Writes Guest Editorial author Dr. Gugala, “The study represented a pioneering effort in sequential intravital imaging of the entire process of calvarial bone repair at a multiscale level and delineated highly dynamic relationships between angiogenesis and osteogenesis.”
Maintaining Skeletal Muscle Strength and Function
A parallel, nonrandomized clinical trial found that endurance training may be an effective intervention for type-2 diabetes mellitus. The myocyte lipid signatures of 27 male patients with type-2 diabetes mellitus and 29 endurance athletes were compared before and after 8 weeks of endurance training or 4 weeks of deconditioning, respectively. The groups differed with respect to intramyocellular fat saturation and palmitate kinetics at baseline, but these values were comparable following the interventions. Patients with diabetes also demonstrated improved insulin sensitivity, cholesterol and triglycerides levels, glycemic control, and metabolic sensing following the intervention4.
Musculoskeletal System in Aging
Researchers investigated whether testosterone supplementation can prevent fractures in men with mild hypogonadism. A total of 5,204 men (45 to 80 years old) with mild hypogonadism and prostate-specific antigen of <3.0 ng/mL received either transdermal testosterone or placebo. At a median follow-up of 3.19 years, the testosterone group had a higher fracture rate than the placebo group (3.5% vs. 2.46%)5. “Divergent behavioral trajectories between the groups, with testosterone likely causing engagement in activities with greater fracture risk, likely accounted for these findings,” notes Dr. Gugala.
What’s New in Musculoskeletal Basic Science is freely available at JBJS.org.
What’s New by Subspecialty
Each month, JBJS publishes a review of the most pertinent studies from the orthopaedic literature in a select subspecialty. To read the reports, visit the What’s New by Subspecialty collection at JBJS.org.
Recent OrthoBuzz posts include: What’s New in Orthopaedic Rehabilitation, What’s New in Shoulder and Elbow Surgery, and What’s New in Hip Surgery.
References
- Lu YZ, Nayer B, Singh SK, Alshoubaki YK, Yuan E, Park AJ, Maruyama K, Akira S, Martino MM. CGRP sensory neurons promote tissue healing via neutrophils and macrophages. Nature. 2024 Apr;628(8008):604-11.
- Babey ME, Krause WC, Chen K, Herber CB, Torok Z, Nikkanen J, Rodriguez R, Zhang X, Castro-Navarro F, Wang Y, Wheeler EE, Villeda S, Leach JK, Lane NE, Scheller EL, Chan CKF, Ambrosi TH, Ingraham HA. A maternal brain hormone that builds bone. Nature. 2024 Aug;632(8024):357-65.
- Bixel MG, Sivaraj KK, Timmen M, Mohanakrishnan V, Aravamudhan A, Adams S, Koh BI, Jeong HW, Kruse K, Stange R, Adams RH. Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration. Nat Commun. 2024 Jun 4;15(1):4575.
- Mezincescu AM, Rudd A, Cheyne L, Horgan G, Philip S, Cameron D, van Loon L, Whitfield P, Gribbin R, Hu MK, Delibegovic M, Fielding B, Lobley G, Thies F, Newby DE, Gray S, Henning A, Dawson D. Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes. Nat Commun. 2024 May 15;15(1):3690.
- Snyder PJ, Bauer DC, Ellenberg SS, Cauley JA, Buhr KA, Bhasin S, Miller MG, Khan NS, Li X, Nissen SE. Testosterone treatment and fractures in men with hypogonadism. N Engl J Med. 2024 Jan 18;390(3):203-11.
