The Anabolic Effect of Teriparatide is Undermined by Low Levels of High-Density Lipoprotein Cholesterol

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.