Intravenous zolendronic acid is an established anti-resorptive treatment for post-menopausal osteoporosis and is usually well tolerated. Common side effects, including the classical 'acute phase response', are consented for prior to treatment. However, rare but serious adverse reactions to zolendronic acid have been described. We report the case of an older patient with osteoporosis and osteoarthritis who presented within 12 hours of her first zolendronic acid infusion with evidence of a severe acute polyarthritis affecting her peripheral appendicular skeleton, in joints affected by pre-existing osteoarthritis. Despite the prevalence of osteoarthritis, this is the most severe case of polyarthritis following intravenous zolendronic acid to date and only the second reported case. We remind prescribing physicians treating patients with intravenous bisphosphonates, to bear in mind possible rare serious adverse reactions as well as common benign side effects. We postulate age-associated frailty may reduce tolerability to even milder acute phase reactions.