These two case reports illustrate several clinical problems. At first chronic inflammatory bone lesions can mimic bone tumors, soft tissue tumors and haematological malignancies including osteosarcoma, rhabdomyosarcoma and Langerhans-cell-histocytosis [
15]. Diagnostic imaging including MRI and bone scan might not be sufficient enough to make a proper diagnosis [
14]. Findings in diagnostic imaging in the two patients were not different in extent and structure from a cohort of patients with chronic osteomyelitis in whom hypophosphatasia had been excluded [
12,
14]. Therefore the diagnosis often has to be biopsy proven. However, the quality of the biopsy depends significantly on whether representative areas of the lesion are included. Secondly, microbial workup has to be as detailed and as extensive as possible to exclude rare chronic bacterial osteomyelitis and to avoid unnecessary long-term antibiotic treatment [
15]. Thirdly, it shows a dilemma in the care of patients with mild hypophosphatasia or hypophosphatasia traitors. Borderline or slightly reduced alkaline phosphatase values might be overlooked in clinical practice especially because the lower reference range of alkaline phosphatase activity is not defined precisely. In addition, hyperpostaglandinism, which has been demonstrated in hypophosphatasia, might contribute to chronic bone inflammation in this disease [
10,
11]. It is also unclear whether growth hormone therapy might also have played a role in the first patient's inflammatory process. In addition, hypophosphatasia patients do show changes in their bone structure, which can resemble vitamin D resistant rickets or osteomalacia clinically and on x-rays [
4]. Hypophosphatasia patients are prone to bone fractures, but bone inflammation has not been reported in conjunction with osteomalacia or fractures in hypophosphatasia so far. In our cases, even though we can not exclude a contribution of the altered bone structure, inflammatory histologic changes seem to be of a different, supposedly metabolic, nature than structural bone insufficiency alone. Furthermore, minimal and unrecognized trauma might be a trigger factor for the lesions seen in our patients. In healthy individuals one would not expected that bone inflammation might result from such a trauma. However, bone in hypophosphatasia might react differently on the basis of the primary TNSALP and secondary metabolic condition (pyrophosphate, prostaglandins) [
11]. A structurally altered rib cage like pigeon-chest is present in some hypophosphatasia patients and might lead to a repetitive minimal trauma at the costochondral junction. Chest structure, however, was unremarkable in our patients. In addition, since a solitary major rib lesion was present in each of our patients a traumatic origin of the lesion seems to be unlikely, because several adjacent lesions could be expected then. Of note, even though the clavicle is affected in CNO predominantly, rib lesions are rare in our and other CNO cohorts [
17,
12,
18‐
22].
Even though the precise aetiology of the hypophosphatasia patient's chronic bone inflammation is not known, symptomatic anti-inflammatory treatment was the treatment of choice and was effective.