Etiology Understanding Is the Core of Skeletal Diagnosis

Background: The term idiopathic is a non-specific disease label, which fails account for proper etiological understanding. The frequent usage of the term idiopathic may indicate clinical incompetence. We describe a number of patients from our practice with a history of complex bone disorders who were falsely given the term idiopathic by other Institutes. The sole tool used by other Institutes to conclude osteoporosis as a diagnosis is the bone mineral density. Material and Methods: Two Austrian families and one unrelated adult female patient (total number of 12 subjects) have been referred to our department with referral letters confirming the diagnosis of idiopathic osteoporosis. All patients manifested a diverse constellation of skeletal deformities. In all these patients, regular courses of anti-resorptive treatment plus calcium and vitamin D supplements. These have been excessively prescribed. Results: Our diagnostic process which is based heavily on detailed clinical and radiological phenotypic characterizations, we refuted the diagnosis of idiopathic osteoporosis for all patients because of the clear-cut clinical features. For the first family, we suggested the diagnosis of a novel type of mucopolysaccharidosis (the genetic results confirmed the diagnosis of a novel subtype of mucopolysaccharidosis (through the identification of arylsulfatase K ARSK). For the second family which has been subjected to a lengthy useless investigation for almost more than a decade, we refuted the diagnosis of idiopathic osteoporosis and the whole exome sequencing was consistent with the phenotypic diagnosis Nasu-Hakola disease (heterozygous missense mutations in TYROBP gene). The other unrelated 42-year-old- female patient was correctly diagnosed with Nasu-Hakola disease. Conclusion: The objective of this study is to minimize and suppress the usage of the term idiopathic. It has been imperative to understand the sequence of pathological events that occurred in these families. The core for diagnosis is the etiological understanding, which stemmed from professional conscientiousness. Patients underwent misdiagnosis of idiopathic osteoporosis and were treated extensively with anti-resorptive agents, calcium supplements and vitamin D. Strikingly, these medications resulted in a combination of serious cranial and cerebral lesions because of massive pathological calcifications. Imaging analysis via conventional radiographs, MRI and CT scan showed massive calcifications of the cranial sutures, inter-clinoid ligaments and hyper-calcification of the skull base. Sadly speaking, early onset dementia emerged in connection with sclerosing leukoencephalopathy. We believe that the exogenous toxic effects of the huge amounts of bone supplements consumed by these patients enhanced the pre-existing metabolic bone and cerebral disorders. Our findings can ameliorate the etiological understanding of early onset dementia and other correlated cranial and skeletal lesions.