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Increased Bone Formation and Accelerated Bone Mass Accrual in a Man Presenting with Diffuse Osteosclerosis/High Bone Mass Phenotype and Adenocarcinoma of Unknown Primary.
JBMR Plus 2023 August
A 71-year-old man was referred for evaluation of incidental generalized osteosclerosis. He was found to have a high bone mass (HBM) with an elevated lumbar spine bone mineral density (BMD) Z-score of +5.3. Over an 18-month period, his lumbar spine BMD measured by dual energy X-ray absorptiometry (DXA) had increased by +64% from 1.09 to 1.79 g/cm2 and femoral neck by +21% from 0.83 to 1.01 g/cm2 . Biochemical markers of bone turnover were markedly increased (serum propeptide of type 1 collagen and urine telopeptides greater than 10-times normal). The high bone formation and increased skeletal calcium acquisition resulted in profound hypocalcemia (low serum calcium 1.88 mmol/L) and hypocalciuria (low urinary calcium <0.2 mmol/day). Positron emission tomography (PET) with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (FDG) confirmed diffuse osteosclerosis without focal areas of abnormal FDG uptake in the skeleton or elsewhere to suggest either an underlying primary malignancy or metastatic disease. Bone biopsy showed markedly sclerotic woven and lamellar bone. The marrow space was devoid of typical bone cells and adipocytes and instead was filled by fibromyxoid stroma, infiltrated by small clusters of tumor cells. Bone histomorphometry and micro-computed tomography demonstrated an elevated trabecular bone volume and trabecular plate thickness. The bone disorder in this case is unique and raises the possibility of a new yet undefined novel anabolic paracrine factor (or factors) secreted by an adenocarcinoma of unknown primary that resulted in dramatic increases in BMD, HBM, and radiological osteosclerosis. The differential diagnosis and potential mechanisms responsible for the HBM are discussed. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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