Smoking is a known risk factor for fractures. However, the role of confounding factors, in particular physical activity and muscle forces, has not been systemically assessed. Moreover, virtually all studies in the past have relied upon dual x-ray absorptiometry, a method that does not yield anatomically accurate information. Therefore, we have organized a cohort study to compare bone strength indicators (BSI) in non-smokers and smokers that were matched for physical activity, leg muscle size and maximal muscle force. We hypothesised that BSI values in smokers are reduced and that this is aggravated with increasing age and smoking history. In 41 smokers (mean age: 41.0; SD: 16.1 years) and 53 non-smokers (47.5±18.2 years), the tibia and radius were scanned by peripheral quantitative computed tomography (pQCT). In line with our initial hypothesis, BSI values for trabecular bone mineral density and epiphyseal bone mineral content were lower in young smokers (229 (95% C.I.: 212-245) mg/cm³ and 362 (334-389) mg/mm, respectively) than in young control participants (278 (257-300) mg/cm³ and 422 (387-457) mg/mm, respectively; p-values 0.002 and 0.008 respectively, ANOVA). Surprisingly, however, such an age-related decline in these parameters was not observed in smokers. As a result the difference in BSI values disappeared in people of 60 years between smokers (260 (239-282) mg/cm³ and 397 (362-432) mg/mm) and non-smokers (246 (230-263) mg/cm³ and 370 (344-398) mg/mm) and independent of their smoking history (R² ranging from 0.000 – 0.021). These results suggest that smoking interferes with osteo-regulatory signals at young age, possibly via factors as oxidative stress and/or other substances in cigarette smoke. This interference of smoking with bone homeostasis wanes with age, suggesting that regulation of bone homeostasis is altered during ageing in smokers.