title: The anabolic effect of teriparatide is undermined by low levels of high-density lipoprotein cholesterol.
abstract: Intermittent parathyroid hormone (PTH) administration has a potent ability to increase bone mass, regardless of underlying conditions or species. A recent study using LDLR(-/-) mice showed that the anabolic effect of PTH was blunted by hyperlipidemia, whereas PTH anabolism was rescued by enhancement of high-density lipoprotein cholesterol (HDL-C) function. We conducted a retrospective longitudinal study to determine whether lipid profiles also affect the anabolic effect of intermittent PTH treatment in humans. Fifty-two patients (8 males and 44 females, ages 38-85 years) with severe osteoporosis who had been treated with teriparatide (TPTD, recombinant human PTH(1-34) for 12 months were studied at Severance Hospital, Yonsei University. C-telopeptide (CTX) and osteocalcin (OCN) were measured at 0, 3, and 12 months; and total cholesterol, triglycerides, and HDL-C were measured at baseline. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at 0 and 12 months. Lumbar spine BMD increased significantly after 12 months of treatment with TPTD (10.0 ± 9.3%, p < 0.001). Initial 3-month changes in CTX and OCN levels revealed positive correlations with the increase in lumbar BMD (r = 0.546, p = 0.001 and r = 0.500, p = 0.006, respectively). Moreover, percentage change in lumbar BMD at 12 months showed a negative correlation with baseline total cholesterol (r = -0.438, p = 0.009) and a positive correlation with HDL-C (r = 0.498, p = 0.016). A smaller 3-month increase in OCN and a lower HDL-C level at baseline were associated with a smaller lumbar BMD increase after TPTD treatment, even after adjustment for age, sex, and other confounding factors (β = 0.462, p = 0.031 for ΔOCN and β = 0.670, p = 0.004 for HDL-C). Plasma levels of lipids, especially HDL-C, seem to be associated with the extent of osteoanabolic effects of TPTD in humans.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, Pusan National University, Busan, Korea, puritystar@hanmail.net.
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Kim
authors.forename: Kwang Joon
authors.initials: KJ
authors.lastname: Kim
authors.forename: In Joo
authors.initials: IJ
authors.lastname: Kim
authors.forename: Sung-Kil
authors.initials: SK
authors.lastname: Lim
authors.forename: Yumie
authors.initials: Y
authors.lastname: Rhee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045930:Anabolic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy*; D012189:Retrospective Studies; D019379:Teriparatide / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D045930:Anabolic Agents; D050071:Bone Density Conservation Agents; D008076:Cholesterol, HDL; D019379:Teriparatide