What’s New in Musculoskeletal Basic Science 2022

Recent groundbreaking studies are summarized in the JBJS Guest Editorial “What’s New in Musculoskeletal Basic Science,” now available at JBJS.org. Here, we spotlight the 5 most intriguing reports, as selected by author Zbigniew Gugala, MD, PhD. 

Pain Resolution 

One recent study examined the role of macrophages in the resolution of inflammatory pain¹. Carrageenan-induced hyperalgesia as a transient pain model in mice was used. As Guest Editorial author Dr. Gugala notes, “this pioneering study identifies a vesicle-mediated mitochondrial transfer between macrophages and the dorsal root ganglia (DRG) sensory neurons during timely resolution of inflammatory pain, thereby offering a novel approach to chronic pain therapy.” 

Skeletal Stem Cell Biology  

In a study using lineage-tracing mice, researchers demonstrated that the expression of osteolectin (Oln) in leptin receptor (LepR)-positive marrow stroma localizes the Oln-positive cells in the periarteriolar and the Oln-negative cells in the perisinusoidal areas of bone marrow². The results of this investigation showed “that the periarteriolar niche in adult bone marrow cooperatively regulates osteogenesis and lymphopoiesis and depends on mechanical stimulation,” writes Dr. Gugala. 

Bone and Cartilage Remodeling  

A recent investigation helps expand our understanding of musculoskeletal diseases associated with dysregulated bone remodeling³. Using real-time imaging of cellular dynamics in the tibiae of living mice, researchers observed that osteoclasts may not, as initially thought, undergo apoptosis after their bone resorptive function ceases. Rather, these multinucleated cells may split into “daughter cells,” called osteomorphs, and recycle to osteoclasts. This process is regulated by the receptor activator of nuclear factor kappa-B ligand (RANKL). The study findings, notes Dr. Gugala, “may explain clinically observed accelerated bone loss following discontinuation of denosumab, an inhibitor RANKL.” 

Cognitive Decline and Bone Health 

Investigators examined the relationship between cognitive decline and osteoporosis and fracture risk⁴. A cohort of 2,361 elderly patients were recruited from the Canadian Multicentre Osteoporosis Study and followed for 10 years. In women, cognitive decline was associated with bone loss, independent of age, education, comorbidities, and lifestyle factors. In addition, a clinically important cognitive decline over 5 years was associated with an increased incidence of fracture over 10 years. 

Vitamin D Supplementation and Bone Health 

An ancillary study of 25,871 participants in the Vitamin D and Omega-3 Trial (VITAL) found that, compared to placebo, vitamin D supplementation (2,000 IU per day) did not significantly lower the risk of total fractures, nonvertebral fractures, or hip fractures in middle-aged and older adults (≥55 years in women and ≥50 years in men)⁵. Subgroup analysis demonstrated no modification of fracture incidence with vitamin D supplementation according to patients’ baseline characteristics, such as age, sex, race or ethnic group, body mass index, or even serum 25-hydroxyvitamin D levels. Of note, study participants were not recruited because of vitamin D deficiency, low bone mass, or osteoporosis. 

“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 Replacement.”  

References 

1. van der Vlist M, Raoof R, Willemen HLDM, Prado J, Versteeg S, Martin Gil C, Vos M, Lokhorst RE, Pasterkamp RJ, Kojima T, Karasuyama H, Khoury-Hanold W, Meyaard L, Eijkelkamp N. Macrophages transfer mitochondria to sensory neurons to resolve inflammatory pain. Neuron. 2022 Feb 16;110(4):613-626.e9.  
2. Shen B, Tasdogan A, Ubellacker JM, Zhang J, Nosyreva ED, Du L, Murphy MM, Hu S, Yi Y, Kara N, Liu X, Guela S, Jia Y, Ramesh V, Embree C, Mitchell EC, Zhao YC, Ju LA, Hu Z, Crane GM, Zhao Z, Syeda R, Morrison SJ. A mechanosensitive peri-arteriolar niche for osteogenesis and lymphopoiesis. Nature. 2021 Mar;591(7850):438-44.  
3. McDonald MM, Khoo WH, Ng PY, Xiao Y, Zamerli J, Thatcher P, Kyaw W, Pathmanandavel K, Grootveld AK, Moran I, Butt D, Nguyen A, Corr A, Warren S, Biro M, Butterfield NC, Guilfoyle SE, Komla-Ebri D, Dack MRG, Dewhurst HF, Logan JG, Li Y, Mohanty ST, Byrne N, Terry RL, Simic MK, Chai R, Quinn JMW, Youlten SE, Pettitt JA, Abi-Hanna D, Jain R, Weninger W, Lundberg M, Sun S, Ebetino FH, Timpson P, Lee WM, Baldock PA, Rogers MJ, Brink R, Williams GR, Bassett JHD, Kemp JP, Pavlos NJ, Croucher PI, Phan TG. Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption. Cell. 2021 Apr 1;184(7):1940.  
4. Bliuc D, Tran T, Adachi JD, Atkins GJ, Berger C, van den Bergh J, Cappai R, Eisman JA, van Geel T, Geusens P, Goltzman D, Hanley DA, Josse R, Kaiser S, Kovacs CS, Langsetmo L, Prior JC, Nguyen TV, Solomon LB, Stapledon C, Center JR; Canadian Multicentre Osteoporosis Study (CaMos) Research Group. Cognitive decline is associated with an accelerated rate of bone loss and increased fracture risk in women: a prospective study from the Canadian Multicentre Osteoporosis Study. J Bone Miner Res. 2021 Nov;36(11):2106-15. 
5. LeBoff MS, Chou SH, Ratliff KA, Cook NR, Khurana B, Kim E, Cawthon PM, Bauer DC, Black D, Gallagher JC, Lee IM, Buring JE, Manson JE. Supplemental vitamin D and incident fractures in midlife and older adults. N Engl J Med. 2022 Jul 28;387(4):299-309.