Hypercalcemia After Cosmetic Oil Injections: Unraveling Etiology, Pathogenesis, and Severity

Abstract

Intramuscular injections of paraffin oil can cause foreign body granuloma formation and hypercalcemia. Macrophages with the ability to produce high levels of 1,25(OH)2D3 may induce the mineral disturbance, but no major series of patients have been published to date. Here, medical history, physical evaluation, biochemical, and urinary analysis for calcium homeostasis were obtained from 88 males, who 6 years previously had injected paraffin or synthol oil into skeletal muscle. Moreover, granuloma tissue from three men was cultured for 48 hours ex vivo to determine 1,25(OH)2D3 production supported by qPCR and immunohistochemistry of vitamin D metabolism and immune cell populations after treatment with 14 different drugs. The 88 men were stratified into men with hypercalcemia (34%), whereas normocalcemic men were separated into men with either normal (42%) or suppressed parathyroid hormone (PTH) (24%). All men had high calcium excretion, and nephrolithiasis was found in 48% of hypercalcemic men, 22% of normocalcemic men with normal PTH, and 47% of normocalcemic men with suppressed PTH. Risk factors for developing hypercalcemia were oil volume injected, injection of heated oil, high serum interleukin‐2 receptor levels, and high urine calcium. High 1,25(OH)2D3/25OHD ratio, calcium excretion, and low PTH was associated with nephrolithiasis. The vitamin D activating enzyme CYP27B1 was markedly expressed in granuloma tissue, and 1,25(OH)2D3 was released in concentrations corresponding to 40% to 50% of the production by human kidney specimens. Dexamethasone, ketoconazole, and ciclosporin significantly suppressed granulomatous production of 1,25(OH)2D3. In conclusion, this study shows that injection of large oil volumes alters calcium homeostasis and increases the risk of nephrolithiasis. Hypercalciuria is an early sign of disease, and high granulomatous 1,25(OH)2D3 production is part of the cause. Prospective clinical trials are needed to determine if ciclosporin, ketoconazole, or other drugs can be used as prednisolone‐sparing treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).

Delayed oleoma formation with injection of oil-suspended testosterone: A case report and review of pathogenesis

“…Besides formation of granulomatous cysts, there have been reports of more severe complications such as hypercalcemia and necrosis at the site of injection using these suspension mediums. 3 , 4 Eldrup et al 3 found that injecting large amounts of oil placed individuals at higher risk for abnormalities in calcium homeostasis, predisposing them to hypercalcemia and nephrolithiasis. Other side effects associated with intramuscular injection of oil include pain, infections, abscesses, chronic wounds, accidental intravenous injections leading to formation of emboli, long-term muscle atrophy and a decrease in muscular volume as well as local swelling and changes in lymph nodes.…”

Possible Relevance of Soluble Luteinizing Hormone Receptor during Development and Adulthood in Boys and Men

“…First-trimester human fetal tissue was collected from women donating the tissue after a scheduled provoked abortion. Fetal kidney and fetal adrenal gland tissue were cultured in a hanging drop model, described in detail previously, and media was collected for analyses [24,25] (Ethical committee approval: H-1-2012-007).…”

Case report: Death caused by multi-organ metastatic calcifications as a result of intramuscular injections with paraffin oil

“…In recent years, a dangerous trend among male bodybuilders has arisen where cosmetic oil is injected subcutaneously and intramuscularly with the purpose of increasing muscle volume. Several studies have described multiple complications occurring years after the injections, where some men develop severe hypercalcemia among a range of other serious organ effects such as nephrolithiasis and renal failure ( Sølling et al, 2018 ; Tachamo et al, 2018 ; Eldrup et al, 2021 ). The clinical presentation is in most cases dominated by the symptoms of hypercalcemia with gastrointestinal symptoms, nausea and renal stones with the addition of pain and swelling from injection sites in the extremities ( Eldrup et al, 2021 ; Sisti et al, 2020 ).…”

“…Several studies have described multiple complications occurring years after the injections, where some men develop severe hypercalcemia among a range of other serious organ effects such as nephrolithiasis and renal failure ( Sølling et al, 2018 ; Tachamo et al, 2018 ; Eldrup et al, 2021 ). The clinical presentation is in most cases dominated by the symptoms of hypercalcemia with gastrointestinal symptoms, nausea and renal stones with the addition of pain and swelling from injection sites in the extremities ( Eldrup et al, 2021 ; Sisti et al, 2020 ). The current understanding of the disease proposes that hypercalcemia can lead to end stage kidney disease (ESKD) ( Walker and Shane, 2022 ),…”