E-Poster Presentation ESA-SRB-ANZBMS 2021

Accelerated diffuse osteosclerosis, high bone mass phenotype and hungry bone syndrome in a man with adenocarcinoma of unknown primary (#36)

Terry Diamond 1 , Carl Bryant 2 , Richard Quinn 3 , Fiona Bonar 4 , Paul A Baldock 5 , Michelle M McDonald 5 , Shejil Kumar 1
  1. Endocrinology Department, St George Public Hospital, SYDNEY, New South Wales, Australia
  2. Radiology Department, St George Private Hospital, Sydney, New South Wales, Australia
  3. Nuclear Medicine Department, St George Private Hospital, Sydney, New South Wales, Australia
  4. Anatomical Pathology Department, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia
  5. Bone Biology Unit, Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia

A 71-year-old man was referred for evaluation of incidental generalised osteosclerosis. He was found to have high bone mass (HBM) with an elevated lumbar spine bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) (1.79 g/cm2) (Z-score +4.6)), a dramatic increase of 62.7% compared to 18-months prior. Left femoral neck BMD also increased by 17.8% from 0.83 g/cm2 to 1.01 g/cm2. Lumbar spine BMD measured by quantitative computed tomography (QCT) was 416.4 mg/cm3 (Z-score +10.9). Biochemical markers of bone formation and resorption were markedly elevated. Rapid skeletal calcium uptake resulted in profound serum hypocalcaemia (1.88 mmol/L) and hypocalciuria (<0.2 mmol/day) suggestive of hungry bone syndrome (HBS). Screening investigations for acquired causes of osteosclerosis and whole-genome sequencing for common pathogenic sclerostin gene variants were negative. CT pan-scan demonstrated small bilateral pleural effusions. Positron emission tomography (PET) with 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) confirmed diffuse osteosclerosis with no focal abnormal FDG uptake in the skeleton or elsewhere to suggest an underlying primary malignancy or metastatic disease. Bone biopsy showed markedly sclerotic woven and lamellar bone, wide osteoid seams and osteocytic osteolysis. The marrow space was devoid of typical bone cells and adipocytes and instead filled by fibro-myxoid stroma, infiltrated by small clusters of adenocarcinoma tumour cells. Bone histomorphometry demonstrated elevated trabecular bone volume. Adenocarcinoma cells were also discovered in pleural fluid cytology and skin verruca histology. He deteriorated over the following 6-months despite chemo/immunotherapy whilst lumbar spine QCT BMD increased further to 548.9 mg/cm3 (Z-score +13.2). He passed away 9-months post-diagnosis.

The bone disorder in this case is unique and raises the possibility of a novel anabolic factor(s) secreted by an adenocarcinoma of unknown primary resulting in dramatic increases in BMD, HBM and radiological osteosclerosis. The differential diagnosis and potential mechanisms responsible for HBM will be discussed in the presentation.

 

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