Shirin Kalyan1, Patricia Huebbe, Tuba Esatbeyoglu, Petra Niklowitz, Hélène C F Côté, Gerald Rimbach, Dieter Kabelitz. 1. Institutes of Immunology (S.K., D.K.) and Human Nutrition and Food Science (P.H., T.E., G.R.), Christian-Albrechts University Kiel, D-24105 Kiel, Germany; Children's Hospital of Datteln (P.N.), University of Witten-Herdecke, D-45711 Datteln, Germany; and Department of Pathology and Laboratory Medicine (H.C.F.C.), University of British Columbia, Vancouver, British Columbia, Canada V6T 2B5.
Abstract
BACKGROUND: Nitrogen-bisphosphonates (N-BPs) are the most widely used drugs for bone fragility disorders. Long-term or high-dose N-BP use is associated with unusual serious side effects such as osteonecrosis of the jaw, musculoskeletal pain, and atypical fractures of long bones. It has escaped notice that the pathway N-BPs block is central for the endogenous synthesis of coenzyme Q10, an integral enzyme of the mitochondrial respiratory chain and an important lipid-soluble antioxidant. Our objective was to assess the coenzyme Q10 and antioxidant status in relation to N-BP exposure in women with postmenopausal osteoporosis. METHODS: Seventy-one postmenopausal women (age, 73.5 ± 5.5 y) with osteoporosis and no other malignancy were included in this cross-sectional study. Seventeen were treatment naive, 27 were on oral N-BP, and 27 were on i.v. N-BP. RESULTS: Vitamin E γ-tocopherol levels (μmol/mL) were significantly reduced in N-BP users [oral, H(2) = 18.5, P = .02; i.v., H(2) = 25.2, P < .001; mean rank comparisons after Kruskal-Wallis test). Length of time (days) of N-BP exposure, but not age, was inversely associated with the coenzyme Q10/cholesterol ratio (μmol/mol) (β = -0.27; P = .025), which was particularly low for those on i.v. N-BP (mean difference = -35.0 ± 16.9; 95% confidence interval, -65.2 to -4.9; P = .02). CONCLUSION: The degree of N-BP exposure appears related to compromised coenzyme Q10 status and vitamin E γ-tocopherol levels in postmenopausal women with osteoporosis. This phenomenon may link to certain adverse N-BP-associated effects. Confirmation of this would suggest that therapeutic supplementation could prevent or reverse certain complications of long-term N-BP therapy for at-risk individuals.
BACKGROUND:Nitrogen-bisphosphonates (N-BPs) are the most widely used drugs for bone fragility disorders. Long-term or high-dose N-BP use is associated with unusual serious side effects such as osteonecrosis of the jaw, musculoskeletal pain, and atypical fractures of long bones. It has escaped notice that the pathway N-BPs block is central for the endogenous synthesis of coenzyme Q10, an integral enzyme of the mitochondrial respiratory chain and an important lipid-soluble antioxidant. Our objective was to assess the coenzyme Q10 and antioxidant status in relation to N-BP exposure in women with postmenopausal osteoporosis. METHODS: Seventy-one postmenopausal women (age, 73.5 ± 5.5 y) with osteoporosis and no other malignancy were included in this cross-sectional study. Seventeen were treatment naive, 27 were on oral N-BP, and 27 were on i.v. N-BP. RESULTS:Vitamin E γ-tocopherol levels (μmol/mL) were significantly reduced in N-BP users [oral, H(2) = 18.5, P = .02; i.v., H(2) = 25.2, P < .001; mean rank comparisons after Kruskal-Wallis test). Length of time (days) of N-BP exposure, but not age, was inversely associated with the coenzyme Q10/cholesterol ratio (μmol/mol) (β = -0.27; P = .025), which was particularly low for those on i.v. N-BP (mean difference = -35.0 ± 16.9; 95% confidence interval, -65.2 to -4.9; P = .02). CONCLUSION: The degree of N-BP exposure appears related to compromised coenzyme Q10 status and vitamin E γ-tocopherol levels in postmenopausal women with osteoporosis. This phenomenon may link to certain adverse N-BP-associated effects. Confirmation of this would suggest that therapeutic supplementation could prevent or reverse certain complications of long-term N-BP therapy for at-risk individuals.
Authors: Alexandra Fischer; Simone Onur; Petra Niklowitz; Thomas Menke; Matthias Laudes; Gerald Rimbach; Frank Döring Journal: PLoS One Date: 2016-12-01 Impact factor: 3.240
Authors: Hanh H Nguyen; Denise M van de Laarschot; Annemieke JMH Verkerk; Frances Milat; M Carola Zillikens; Peter R Ebeling Journal: JBMR Plus Date: 2018-01-03