A critical review of the anthropological and paleopathological literature on osteopetrosis as an ancient rare disease (ARD).

Abstract Objective A reappraisal of the available evidence of osteopetrosis in the archaeological record as first step in promoting new approaches to rare diseases in paleopathology. Materials and methods Three different approaches are combined: a survey of the last 50 years of bioarchaeological publications; an online search addressing six of the more widely used search engines; macroscopic and radiographic analyses of the human remains from the Neolithic site of Palata 2 (Italy). Results The combined results of the literature survey and the online search identified six cases of osteopetrosis. The majority of search hits place this disease into differential diagnoses. The investigation of the remains from Palata 2, one of the six cases in literature, indicates a non-specific sclerosis of the cranial vault. Conclusions Of the six cases of osteopetrosis, only two, one of the autosomal-recessive type (ARO) and one of the autosomal-dominant type (ADO), are supported by direct osteoarchaeological evidence. Therefore, inaccurate differential diagnoses generate an inflated number of cases in the paleopathological record. Significance This reappraisal calls for a more informed and evidence-based approach to osteopetrosis and, more generally, to rare diseases in paleopathology. Limitations Lack of specific publications on osteopetrosis; more case studies may be present in “gray literature”. Suggestions for further research Cases of osteopetrosis from archaeological and historical collections as well as medical literature are needed to increase knowledge about this rare disease. More precise differential diagnoses are required, particularly when dealing with rare diseases.