Osteoporosis is a diffuse skeletal disorder characterized by decreased bone strength and increased fracture risk. The measure of BMD (bone mineral density) is useful both in the diagnosis of the disorder and for the fracture risk assessment [1]. Nevertheless, this investigation alone is insufficient for making therapeutic decisions. Zoledronic acid is a biphosphonate that plays a role in inhibiting osteoclastic resorption. This treatment is administered yearly through the intravenous route. Considering its toxic effect on the kidney, the treatment is selectively given to patients with a glomerular filtration rate (GFR) above 30 ml/min. Minor secondary effects such as flu symptoms and gastrointestinal upsets are reported. Some less reported effects include arrhythmias [2][3].

Osteomyelitis following zoledronic acid perfusion is not reported in the literature. A series of 3889 patients receiving zoledronic acid perfusion yearly for three years, no case of arthritis was reported. The most frequent side effects were fever, myalgias, flu symptoms, and headache. Nevertheless, we had a significant number of cases with cardiovascular events such as atrial fibrillation, and impaired kidney function [3]. These symptoms generally regress over three days. Febrile reactions were more significant in patients with unexplained raised levels of PTH [4]. Although fever in patients receiving zoledronic acid was explained by elevated CRP and some cytokines like IL6 and TNF alpha, the mechanism of osteomyelitis still remains unexplained [5][6]. The absence of crystals, inflammatory liquid and medullary contrast-enhanced foci on MRI contradicts the possibility of a microcrystalline arthritis. By isolating, for example, the osteoblasts present in osteophytes of the arthrosic knee, and those of the subchondral non-arthrosic joints, Sako et al. showed that the osteoblasts of osteophytes play a role in the degradation process by significantly producing more IL6, IL8 and MMP-13 than non-arthrosic osteoblasts [7]. The amplification mechanism of a degenerative coxopathy thus remains the most feasible in our patient. If this is the case, the local release by inflammatory tissues of inflammatory mediators would have been done by all surrounding tissues: synovitis, bursitis, muscle fascia and bone marrow. This hypothesis is more likely as it has been shown in vivo that IL1-beta is a pivot in joint destruction mechanisms and the principal mediator in enzymatic activation in synergy with TNF alpha in osteoarthritis [8]-[10]. Zoledronic acid could potentiate the macrophagic process that causes the amplification of the inflammatory cascade by acting at all levels of the degenerative process of the bone marrow and the peritendinous bursa?

Otherwise, Suppressor of cytokine signaling-3 (SOCS3) inhibits the Janus kinase (Jaki) and regulates protein degradation and suppression of cytokine signaling. SOCS3 modulates the macrophage response and cytokines such as IL6 and leptin. Zoledronate is an inhibitor of SOCS3 and thus acts in increasing the local inflammatory phenomenon by inhibiting STAT3 and by increasing the local production of IL6 [11]. This matches our hypothesis. In our patient, no treatment was necessary, and the control MRI showed a spontaneous favourable evolution, the restoration of the hip mobility and regression of the inflammatory syndrome. The only intervening event was the administration of zoledronic acid, implying a cause-and-effect reaction.

Aseptic osteomyelitis that abruptly appeared following a zoledronic acid perfusion mimics a likely septic osteoarthritis in this elderly patient. The favourable spontaneous evolution of clinical and paraclinical parameters goes in favour of an isolated event. A cause-and-effect relation is thus drawn out.