TY - JOUR

T1 - Treatment options for hypercalcemia after cosmetic oil injections

T2 - Lessons from human tissue cultures and a pilot intervention study

AU - Yahyavi, Sam Kafai

AU - Theilade, Simone

AU - Hansen, Ditte

AU - Berg, Jais Oliver

AU - Andreassen, Christine Hjorth

AU - Lorenzen, Mette

AU - Jørgensen, Anne

AU - Juul, Anders

AU - Faber, Jens

AU - Eldrup, Ebbe

AU - Jensen, Martin Blomberg

N1 - Publisher Copyright: © 2021 The Authors

PY - 2022

Y1 - 2022

N2 - Objective: Granuloma formation following self-administered cosmetic oil injections can lead to severe hypercalcemia and renal calcifications due to extra-renal vitamin D activation. This translational study aims to identify Prednisolone sparing therapeutics for hypercalcemia after development of granulomatous disease secondary to paraffin oil injections. Materials and methods: Granuloma tissue isolated from five men were cultured ex vivo and treated with selected drugs to block generation of activated vitamin D (1,25(OH)2D3). In a retrospective study, we included data before and during different treatments of 21 men with paraffin oil induced granulomatous hypercalcemia (46 treatment courses) where serum calcium, parathyroid hormone, vitamin D metabolites, creatinine and inflammatory markers were measured. Results: Addition of Ketoconazole or Ciclosporin to granuloma tissue ex vivo culture, significantly suppressed production of 1,25(OH)2D3 after 48 h (both p < 0.05). Prednisolone was the first treatment option in most men and lowered serum levels of ionized calcium after 1, 2, 3 and 6 months compared with baseline (p < 0.05). Ketoconazole or Hydroxychloroquine had no significant effect on serum calcium levels and were unable to reduce the concomitant daily Prednisolone doses (p > 0.05). Azathioprine did not reduce calcium levels. However, addition of Tacrolimus to Prednisolone treatment enabled a reduction in Prednisolone dose after 3 months (p = 0.014), but with no additional effect on calcium homeostasis. Conclusion: This study verifies that Prednisolone is an effective treatment and suggests that calcineurin inhibitors may be used as Prednisolone sparing treatment for paraffin oil-induced granulomatous hypercalcemia. Randomized clinical trials are needed to determine clinical efficacy.

AB - Objective: Granuloma formation following self-administered cosmetic oil injections can lead to severe hypercalcemia and renal calcifications due to extra-renal vitamin D activation. This translational study aims to identify Prednisolone sparing therapeutics for hypercalcemia after development of granulomatous disease secondary to paraffin oil injections. Materials and methods: Granuloma tissue isolated from five men were cultured ex vivo and treated with selected drugs to block generation of activated vitamin D (1,25(OH)2D3). In a retrospective study, we included data before and during different treatments of 21 men with paraffin oil induced granulomatous hypercalcemia (46 treatment courses) where serum calcium, parathyroid hormone, vitamin D metabolites, creatinine and inflammatory markers were measured. Results: Addition of Ketoconazole or Ciclosporin to granuloma tissue ex vivo culture, significantly suppressed production of 1,25(OH)2D3 after 48 h (both p < 0.05). Prednisolone was the first treatment option in most men and lowered serum levels of ionized calcium after 1, 2, 3 and 6 months compared with baseline (p < 0.05). Ketoconazole or Hydroxychloroquine had no significant effect on serum calcium levels and were unable to reduce the concomitant daily Prednisolone doses (p > 0.05). Azathioprine did not reduce calcium levels. However, addition of Tacrolimus to Prednisolone treatment enabled a reduction in Prednisolone dose after 3 months (p = 0.014), but with no additional effect on calcium homeostasis. Conclusion: This study verifies that Prednisolone is an effective treatment and suggests that calcineurin inhibitors may be used as Prednisolone sparing treatment for paraffin oil-induced granulomatous hypercalcemia. Randomized clinical trials are needed to determine clinical efficacy.

KW - Cosmetic oil injections

KW - Extra-renal vitamin D activation

KW - Granuloma

KW - Hypercalcemia

KW - Prednisolone

KW - Tacrolimus

U2 - 10.1016/j.bone.2021.116244

DO - 10.1016/j.bone.2021.116244

M3 - Journal article

C2 - 34757214

AN - SCOPUS:85118693596

VL - 154

JO - Bone

JF - Bone

SN - 8756-3282

M1 - 116244

ER -