Exploring Circulating CD34+ Cells as a Biomarker of Fracture Risk in DMD

Duchenne muscular dystrophy (DMD) is well known for its impact on muscle degeneration, but its association with skeletal fragility, especially in the context of long-term glucocorticoid (GC) use, is equally concerning. In a new study by Sadlowski et al., published in the Journal of Bone and Mineral Research in 2025, researchers investigated whether blood-derived biomarkers—specifically circulating CD34+ cells and related progenitor populations—might help predict fracture risk in boys and young men with DMD on chronic GC therapy.

Rather than relying on invasive bone biopsies, the team explored the translational potential of “liquid biopsy” markers to reflect bone remodeling and angiogenic potential, which is a relevant pursuit given the pressing need for non-invasive risk stratification tools in pediatric and adolescent populations with limited mobility.

This was a single-site, case–control study that enrolled 24 males (aged 8-20 years) with genetically confirmed DMD and chronic GC exposure. Participants were divided into two disease groups: those with osteoporosis (n=14) and those without (n=10). Additionally, the researchers recruited age- and sex-matched healthy controls.

All participants provided blood samples for serum angiogenic factor measurement and peripheral blood mononuclear cell (PBMC) isolation. Investigators then used multiparameter flow cytometry to quantify cell types of interest:

• Preosteoclasts (POCs): CD14+/Stro-1−/CD105−
• Skeletal progenitor cells (SPCs): Stro-1+/CD105+/CD14−/CD45−
• Endothelial/hematopoietic progenitor-like CD34+ cells: CD34+/CD14−/Stro-1−/CD105−

Bone health was assessed both retrospectively and prospectively over a median follow-up of 2.23 years.

One of the most striking findings was that higher circulating percentages of CD34+ cells were associated with prolonged time to next fracture. This association held true even after adjusting for known confounders such as age, pubertal status, prior fractures, glucocorticoid duration, bone density, and hormone therapies. In multivariable accelerated failure time models, higher CD34+ percentages remained independently protective (p = 0.005).

Other notable associations include:

• PDGF-BB (platelet-derived growth factor-BB) levels positively correlated with circulating CD34+ cell percentages (p = 0.0499), echoing mechanisms previously demonstrated in mice, where POC-secreted PDGF-BB supports vascular and skeletal progenitor recruitment.
• Lower SPC percentages and reduced CD140b (PDGFR-β) expression were both associated with increased historical fracture burden (p = 0.010 and p = 0.032, respectively).
• POC percentages, though expected to align with fracture protection, only trended toward significance (p = 0.11).

It’s worth noting that bisphosphonate use was disproportionately higher among participants with osteoporosis (93% vs 20%), which may have influenced angiogenesis and progenitor cell activity in subtle, complex ways.

Why CD34+ Cells Matter

CD34+ cells have long been appreciated as markers of hematopoietic and endothelial progenitors, but their relevance in skeletal biology is gaining traction. In this study, their presence in peripheral blood appeared to be a functional barometer of bone health in DMD. The hypothesis: more CD34+ cells reflect a better capacity for microvascular and osteogenic repair, which are key elements in preventing fractures in a fragile skeleton.

Supporting this notion, prior work has identified CD34+ cells in the periosteum with roles in fracture healing and angiogenesis. This study now provides clinical data suggesting that CD34+ cells may one day guide individualized fracture risk assessments.

While compelling, this pilot study is limited by sample size and the rarity of detectable SPCs, which hindered some analyses. But the direction is promising. If validated in larger cohorts, circulating CD34+ cells, along with PDGF-BB and CD140b MFI, could become pivotal tools in primary fracture prevention for youth with DMD.

A blood-based biomarker would be especially valuable in this population. As DMD survival improves, these tools could help clinicians identify high-risk individuals earlier and tailor bone-protective interventions.

Reference

Sadlowski A, See J, Bharill S, et al. Circulating CD34-positive cells are associated with prolonged time to fracture in people with Duchenne muscular dystrophy on chronic glucocorticoids. J Bone Miner Res. 2025;40(5):617-627. doi:10.1093/jbmr/zjaf041