The Hidden Symptom: Unveiling the Prevalence and Management of Bone Pain in Iron Deficiency

Background Iron deficiency is a global health concern, traditionally associated with fatigue and anemia. Its potential association with specific somatic symptoms, such as bone pain, remains poorly characterized and is not a routine consideration in clinical practice. Objectives This study aimed to assess the prevalence of iron deficiency-associated bone pain, evaluate intravenous iron therapy’s efficacy in reducing pain, and identify predictors of improvement in pain scores. Methods and Materials A prospective cohort study was conducted at the outpatient hematology clinic of Al Nasiriya Teaching Hospital, between March and July 2025. Consecutive eligible patients aged 15-65 with confirmed iron deficiency (ferritin <30 ng/mL) who were prescribed intravenous iron sucrose as part of their standard clinical care were enrolled. The total cumulative dose (500 mg to 1200 mg, per the Ganzoni formula) was administered as smaller doses over multiple sessions per routine practice. The primary outcome was the change in pain intensity measured on the Numeric Pain Rating Scale (NPRS, 0-10) from baseline to six-week follow-up. Secondary outcomes included prevalence of bone pain at baseline, change in ferritin levels, and predictors of pain reduction Results Among the enrolled patients (95.8% female), (29.2%, 95% CI: 21.02 to 39.42) reported bone pain, with the legs being the most common reported site. Patients with bone pain had severely depleted baseline iron stores 6.7 ng/mL (IQR 2.63-11, range 0.7-29). Following intravenous iron therapy, a profound and statistically significant improvement was observed: the median NRS pain score decreased from 9 (IQR 8-9, range 5-10) to 2 (IQR 1-5, range 0-7; p<0.001), representing a 77.8% reduction (p<0.001). This clinical improvement was underpinned by a robust biochemical response, with median ferritin levels rising to 70.5 ng/mL (IQR 56-87, range 34-152; p<0.001). A significant negative correlation was observed between baseline ferritin levels and pain scores (r = -0.464, p = 0.003) and a strong negative correlation between the magnitude of increase in ferritin and the magnitude of decrease in pain scores (r = -0.483, p = 0.002). Multivariable analysis identified two independent predictors of a greater percentage reduction in pain score: baseline anemia (associated with a 36.6% greater reduction; 95% CI: 12.87 to 60.33, p=0.004) and higher post-infusion ferritin levels (0.51% greater reduction per 1 ng/mL increase; 95% CI: 0.01 to 1.01, p=0.046). Conclusion B one pain is a prevalent and under-recognized symptom of iron deficiency. Our findings suggest a strong association between intravenous iron therapy and a significant reduction in pain severity, indicating it may be a highly effective treatment for this symptom. These findings advocate for greater clinical vigilance for this symptom and support a targeted, pathophysiologically-oriented treatment strategy.