Monitoring of Cellular Changes in the Bone Marrow following PTH(1-34) Treatment of OVX Rats Using a Portable Stray-Field NMR Scanner

Abstract

Osteoporosis is characterized by reduction in trabecular bone in conjunction with increased marrow cell adiposity. While these changes occur within weeks, monitoring of treatment efficacy as performed by DEXA is sensitive only to long-term changes. MRI is sensitive to bone marrow changes but is less affordable. In a recent study, we have shown that a stray-field NMR can monitor bone marrow cellular changes that are related to osteoporosis. Objectives. To demonstrate sensitivity of a low-field tabletop NMR scanner to bone marrow dynamics following hormonal treatment in rats. Methods. Two-month-old female rats (n = 36) were ovariectomized (OVX) and dosed for the ensuing 3 or 5 weeks with 20 mg/kg of PTH(1-34). Hind limbs femurs and tibiae were isolated and underwent ex vivo microradiography and histology and NMR relaxometry at 6 weeks (preventive experiment) and 11 weeks (therapeutic treatment experiment) after OVX. Results. OVX rats developed osteoporotic changes including adipogenic marrow compared to Sham and PTH treated rats. T2 and ADC NMR relaxation coefficients were found to correlate with marrow composition. Conclusions. This study suggests that stray-field NMR, an affordable method that is sensitive to the rapid cellular changes in bone marrow, may have a clinical value in monitoring hormonal treatment for osteoporosis.

Intermittent PTH 1–34 administration improves the marrow microenvironment and endothelium-dependent vasodilation in bone arteries of aged rats

“…Previous investigations have made the link between the marrow microenvironment and bone remodeling (8,19,24,28), suggesting paracrine signaling between bone marrow and bone cells. For example, restoration of hematopoietic stem cells in the tibia following intermittent PTH administration in mice served to augment bone volume (28).…”

“…), the numbers of hematopoietic stem cells and adipocytes were partially increased and decreased, respectively, compared with the Bmi1null, vehicle-treated animals (28). Furthermore, PTH 1-34 administration suppressed and prevented adipogenesis in the marrow microenvironment of ovariectomized rats (19). Thus, it is speculated that intermittent PTH administration modulates the accessory cells in the marrow (24), which may contribute to bone accrual.…”

“…Thus, enhanced production of proinflammatory cytokines may contribute to the diminished bone vascular function observed in old animals. Furthermore, the positive impact of intermittent PTH administration on the marrow microenvironment (19,28) suggests a similar beneficial outcome for the bone vasculature. The purpose of the present study was to determine whether the marrow microenvironment, via proinflammatory cytokine production, alters vasodilation in the femoral PNA in young and old rats.…”

Quantitative MR Analysis of Changes in the Radius Bone Marrow in Osteoporosis

“…A possible mitigation strategy may be the use of low-cost low-field MRI systems. Indeed, Sarda et al and Hillel et al [ 19 , 20 ] used animal models and suggested that stray field NMR can be used to detect changes in bone marrow composition, potentially enabling screening and treatment follow-up [ 19 , 20 ]. Importantly, translation of such works to humans requires a target bone that can easily be probed using such scanners.…”