Widely distributed osteosclerosis is an unusual radiographic finding with multiple causes. A 42-year-old pre-menopausal Spanish woman gradually acquired dense bone diffusely affecting her axial skeleton and focally affecting her proximal long bones. Systemic lupus erythematosus diagnosed in adolescence had been well controlled. She had not fractured or received antiresorptive therapy, and was hepatitis C virus antibody negative. Family members had low bone mass. Lumbar spine BMD measured by dual-photon absorptiometry at age 17 years, while receiving glucocorticoids, was 79% the average value of age-matched controls. From ages 30 to 37 years, DXA BMD z-scores steadily increased in her lumbar spine from +3.8 to +7.9, and femoral neck from -1.4 to -0.7. Serum calcium and phosphorus levels were consistently normal, 25OHD <20 ng/mL, and PTH sometimes slightly increased. Her reduced eGFR was 38-55 mls/min. Hypocalciuria likely reflected positive mineral balance. During increasing BMD, turnover markers (serum bone-ALP, PINP, osteocalcin, and CTX, and urinary NTX) were 1.6- to 2.8-fold above the reference limits. Those of bone formation seemed increased more than those of resorption. FGF-23 was slightly elevated, perhaps from kidney disease. Serum OPG and TGFβ1 levels were normal, but sclerostin (SOST) and RANKL were elevated. Serum multiplex biomarker profiling confirmed a high level of SOST and RANKL, whereas DKK-1 seemed low. Matrix metalloproteinases-3 and -7 were elevated. Iliac crest biopsy revealed tetracycline labels, no distinction between thick trabeculae and cortical bone, absence of peritrabecular fibrosis, few osteoclasts, and no mastocytosis. Then, for the past three years, BMD z-scores steadily decreased. Skeletal fluorosis, mastocytosis, myelofibrosis, hepatitis C-associated osteosclerosis, multiple myeloma, and aberrant phosphate homeostasis did not explain her osteosclerosis. Mutation analysis of the LRP5, LRP4, SOST, and osteopetrosis genes was negative. Microarray showed no notable copy number variation. Perhaps her osteosclerosis reflected an interval of autoimmune-mediated resistance to SOST and/or RANKL. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
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