title: Nitrogen-bisphosphonate therapy is linked to compromised coenzyme Q10 and vitamin E status in postmenopausal women.
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).
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Shirin
authors.initials: S
authors.lastname: Kalyan
authors.forename: Patricia
authors.initials: P
authors.lastname: Huebbe
authors.forename: Tuba
authors.initials: T
authors.lastname: Esatbeyoglu
authors.forename: Petra
authors.initials: P
authors.lastname: Niklowitz
authors.forename: Hélène C F
authors.initials: HC
authors.lastname: Côté
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
authors.forename: Dieter
authors.initials: D
authors.lastname: Kabelitz
mesh_terms: D000368:Aged; D001259:Ataxia / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology; D003430:Cross-Sectional Studies; D004164:Diphosphonates / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D028361:Mitochondrial Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology; D018908:Muscle Weakness / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology; D009584:Nitrogen / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D017698:Postmenopause / Q000097:blood / Q000187:drug effects; D011379:Prognosis; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000097:blood / Q000172:deficiency; D014810:Vitamin E / Q000097:blood*; D014811:Vitamin E Deficiency / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D004164:Diphosphonates; D014451:Ubiquinone; D014810:Vitamin E; C024989:coenzyme Q10; D009584:Nitrogen