Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis.
BACKGROUND
Abaloparatide is a novel synthetic peptide analog of parathyroid hormone-related protein (PTHrP) that is currently being developed as a potential anabolic agent in the treatment of postmenopausal osteoporosis.


OBJECTIVE
This study sought to assess the effects of abaloparatide on bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck in postmenopausal women with osteoporosis.


METHODS
Multi-center, multi-national, double-blind placebo controlled trial in which postmenopausal women were randomly assigned to receive 24 weeks of treatment with daily sc injections of placebo, abaloparatide, 20, 40, or 80 μg, or teriparatide, 20 μg. A 24-week extension was also performed in a subset of subjects.


METHODS
Postmenopausal women with osteoporosis (n = 222).


METHODS
BMD by dual-x-ray absorptiometry and biochemical markers of bone turnover.


RESULTS
At 24 weeks, lumbar spine BMD increased by 2.9, 5.2, and 6.7% in the abaloparatide, 20-, 40-, and 80-μg groups, respectively, and 5.5% in the teriparatide group. The increases in the 40- and 80-μg abaloparatide groups and the teriparatide group were significantly greater than placebo (1.6%). Femoral neck BMD increased by 2.7, 2.2, and 3.1% in abaloparatide, 20-, 40-, and 80-μg groups, respectively, and 1.1% in the teriparatide group. The increase in femoral neck BMD with abaloparatide, 80 μg was significantly greater than placebo (0.8%). Total hip BMD increased by 1.4, 2.0, and 2.6% in the abaloparatide, 20-, 40-, and 80-μg groups, respectively. The total hip increases in the 40- and 80-μg abaloparatide groups were greater than both placebo (0.4%) and teriparatide (0.5%).


CONCLUSIONS
Compared with placebo, 24 weeks of daily sc abaloparatide increases BMD of the lumbar spine, femoral neck, and total hip in a dose-dependent fashion. Moreover, the abaloparatide-induced BMD increases at the total hip are greater than with the marketed dose of teriparatide. These results support the further investigation of abaloparatide as an anabolic therapy in postmenopausal osteoporosis.
Endocrine Unit, Department of Medicine (B.Z.L.), Massachusetts General Hospital,, Harvard Medical School, Boston, Massachusetts 02114; Radius Health Inc. (L.S.O., K.B., K.M., C.R.L., G.H.), Waltham, Massachusetts 02451; Centre for Diabetes & Endocrine Care (P.K.), Karnataka 560043, India; and Instituto de Diagnóstico e Investigaciones Metabólicas (J.R.Z.), Buenos Aires, Argentina.
Benjamin Z
BZ
Leder
Louis St L
LS
O'Dea
José R
JR
Zanchetta
Prasana
P
Kumar
Kathleen
K
Banks
Kathleen
K
McKay
C Richard
CR
Lyttle
Gary
G
Hattersley
D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology* / Q000627:therapeutic use; D011859:Radiography; D019379:Teriparatide / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D044162:Parathyroid Hormone-Related Protein; D019379:Teriparatide; C000596789:abaloparatide