The five “Ws” for bone pain due to the administration of granulocyte-colony stimulating factors (G-CSFs)

Granulocyte-colony stimulating factors (G-CSFs) are commonly employed in clinical practice. The most relevant adverse event of G-CSF administration is bone pain. Approximately 20% of cancer patients experienced bone pain with the administration of prophylactic daily G-CSFs (lenograstim and filgrastim). The reported incidence of bone pain in cancer patients undergoing pegfilgrastim prophylaxis ranged from 25% to 38%. In healthy donors the incidence of bone pain was higher than in cancer patients, ranging from 52% to 84%. There are four main causes of G-CSF related bone pain: bone marrow quantitative and qualitative expansion, peripheral nociceptor sensitization to nociceptive stimuli, modulation of immune function and direct effect on bone metabolism. For the prevention and treatment of bone pain occurring after or during GCSFs administration, acetaminophen and nonsteroidal anti-inflammatory agents are commonly used as first-line treatment; antihistamines, opioids and dose reduction of G-CSFs are considered as second line therapy. The only randomized clinical trial conducted for the prevention and treatment of G-CSF induced bone pain showed the efficacy of naproxen in reducing the incidence, the severity and the duration of bone pain induced by the administration of pegfilgrastim.