Extreme PTH-Independent Hypercalcemia Mediated by a Rare Non-Osteoclastic Osteolysis Mechanism in Newly Diagnosed High-Risk Biclonal IgA Multiple Myeloma: Temporal Association with the Second Dose of Moderna mRNA-1273 COVID-19 Vaccine.

We report the first documented case of extreme, intact parathyroid hormone (PTH)-independent hypercalcemia mediated by a rare non-osteoclastic bone remodeling mechanism in a 65-year-old Puerto Rican woman, detected within 24 h of the second dose of the Moderna mRNA-1273 COVID-19 vaccine and leading to the diagnosis of high-risk biclonal IgA plasma cell myeloma (R-ISS Stage III). Peak serum calcium reached 17.4 mg/dL with concurrent hyperphosphatemia, normal lactate dehydrogenase (LDH), and without marrow osteoclasts or osteolytic lesions, findings inconsistent with classical cancer-associated hypercalcemia. Hypercalcemia resolved within eight days with supportive treatment alone, remaining durably normal nine months later. The temporal proximity to vaccination, together with the biochemical-histopathological profile, generates the hypothesis, without implying causation, that a vaccine-induced innate immune response triggered a rare inflammatory osteocytic perilacunar/canalicular remodeling. The biclonal gammopathy, Clone-1 (normal karyotype, CD33+, OCT-2+, MYC-, CD19+, PAX5-) and Clone-2 (complex high-risk karyotype, OCT-2-, MYC+low, CD19-), suggests epigenetic rather than genomic drivers in the predominant clone. This case proposes a novel mechanistic hypothesis for vaccine-associated hypercalcemia and generates testable questions that warrant prospective investigation.