Glucocorticoid treatment, a major cause of drug-induced osteoporosis and fractures, is widely used to treat inflammatory conditions and diseases. By contrast, mechanical loading increases bone mass and decreases fracture risk. With these relationships in mind, we investigated whether mechanical loading interacts with GC treatment in bone

In GC-treated patients, long-term GC treatment increases fracture risk by increasing bone resorption and decreasing bone formation. However, the risk of fracture is increased even before osteoporosis is established. This phenomenon indicates that, in addition to reducing bone mass, GCs deteriorate bone quality in general.

In studies of osteocytic cell lines, mechanical loading (fluid flow shear stress/pulsating fluid flow) inhibited GC-induced apoptosis. In a rat study, mechanical loading (vibration) partly inhibited GC-induced loss of trabecular bone.

In patients treated with GCs, mechanical loading (resistance training, treadmill exercise or jumps) can prevent GC-induced vertebral osteoporosis and, at least partly, restore BMD of the whole body, femur neck, lumbar vertebra, and radius.

We hypothesized that loading can counteract the detrimental effects in mouse bone of high-dose prednisolone, the most commonly used GC for treatment of inflammatory disease. Therefore, we investigated the effect of prednisolone on bone with and without mechanical loading.

Results

Long-term GC treatment results in GC-induced osteoporosis; however, osteoporosis can be mitigated by increased bone formation, a process that can be induced by mechanical loading. With these relationships in mind, we investigated whether mechanical loading interacts with GC treatment in bone.

To test this hypothesis, we used well-established protocols for axial mechanical load and GC treatment (i.e. prednisolone). We found that mechanical loading alone increased trabecular BMD, but prednisolone treatment alone did not alter trabecular BMD in control tibiae without the external mechanical loading.

Using the same mouse strain as we did, a recent study also found that prednisolone treatment did not alter trabecular bone, specifically femoral bone.

However, other studies using the same mouse strain found that prednisolone treatment significantly decreased trabecular bone in vertebrae. These uneven findings suggest that prednisolone effects for trabecular bone may be site- and/or mouse strain-specific.

We found that prednisolone inhibited the loading-induced increase of trabecular volumetric BMD by 57%, revealing that the loading response is less efficient in trabecular bone in the presence of prednisolone. We used a supra-pharmacological dose of prednisolone, but it is possible that mechanical loading could increase trabecular bone more if the prednisolone dose was lower