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.