Teriparatide in Osteoporosis

1. Clinical Application of Teriparatide in
Fracture Prevention
Prepared by Dr Madan Mohan
Based on an Investigation performed at the
Department of Orthopaedic Surgery,
New York University Medical Center,
New York, NY
JBJS REVIEWS 2019;7(1):e10 · http://dx.doi.org/10.2106/JBJS.RVW.18.00052

2. • Fractures are generally more common in men than women
until the age of 55 years, whereupon a shift in the sex
specificity of fracture incidence emerges.
• The increasing likelihood of fracture with advanced age is
often attributed to the osteoporotic changes in bone
quality that occur with age.
• Specific factors that increase the likelihood of fracture
include a history of fracture after the age of 50 years, high
serum phosphate, the use of selective serotonin receptor
inhibitors, decreased bone mineral density (BMD) in the
right arm, obesity, coexisting diseases (e.g., inflammatory
rheumatic disease, chronic kidney disease), and the use of
oral corticosteroids

3. •in patients above 50years of age who have a history
of fragility fracture of the hip or vertebra, the 10-
year risk for secondary fracture reaches 20%.
•Accordingly, the strategy for the treatment of a first
fracture often incorporates medication aimed to
reduce the risk of secondary fracture

4. • PTH, an anabolic drug for osteoporosis, plays an important
role in regulating calcium and phosphate metabolism and
physiological bone remodeling.
• Clinically, there are 2 recombinant human PTH analogues,
PTH 1-84, a full-length recombinant protein, andPTH1-34
(also known as teriparatide), a 1-34 fragment of PTH that
preserves most of the biological activities of PTH.
• Teriparatide, under the brand name Forteo, first received
approval for marketing by the U.S. Food and Drug
Administration(FDA) in 2002 as an anabolic agent for
osteoporosis treatment in both men and women who are
at high risk of fracture.

5. •Teriparatide can increase the BMD of the
lumbar spine and femur (an effect that is
enhanced with dosage, treatment duration,
and younger age at therapeutic intervention
and is preventative against fracture.
•Teriparatide is also recommended as first-line
treatment for glucocorticoid-induced
osteoporosis and shows greater efficacy for
increasing BMD than oral bisphosphonates do
in this application

6. Mechanistically, the administration of a low dose
of PTH demonstrably increases osteoblast
activity, bone formation, and lining-cell
differentiation and also decreases the
apoptosis of osteoblasts, which contributes to
an overall elevation of bone mass and
improvement in bone microstructure

7. •Evidence from systematic reviews and meta-
analyses suggests that teriparatide is effective
for preventing vertebral and nonvertebral
fractures in osteoporotic patients with multiple
preexisting risk factors, including
postmenopause status, glucocorticoid
treatment, and chronic kidney disease.
•However, the evidence also suggests that
teriparatide fails to prevent site-specific
fractures at the wrist and hip

8. •In Europe, 6% of men and 21% of
women 50 to 84 years of age had
osteoporosis in 20102.
•Worldwide, osteoporosis causes 8.9
million fractures every year

9. •Bisphosphonates are the first-line treatment
for fracture prevention in patients with
osteoporosis, and teriparatide is approved for
the treatment of severe osteoporosis or
following bisphosphonate failure.
•Teriparatide also is effective for the treatment
of glucocorticoid-induced osteoporosis

10. Sequential treatment with abaloparatide
(80 mg/day) for 18 months followedby
alendronate (70mg/week) for 6 months
resulted in greater increases in BMD and
fracture reduction in women with
postmenopausal osteoporosis

11. •Teriparatide is superior to PTH 1-84 for the
prevention of vertebral and nonvertebral fractures in
postmenopausal women with severe osteoporosis
•Teriparatide has been suggested for use in
osteoporotic patients who have undergone spinal
fusion surgery because it has been associated with
elevation of spinal fusion rates, improvement of the
bone-implant interface, and reduction of the rate of
screw loosening

12. • A new anabolic drug, abaloparatide, was cleared for marketing by
theFDA in 2017 for postmenopausal women with osteoporosis who
are at high risk for fracture.
• Abaloparatide can improve bone formation, bone mass, lumbar
vertebral strength, and maintenance of bone quality and seems to be
more effective than teriparatide in these respects
• Abaloparatide, a 34- amino-acid recombinant PTH-related peptide
(PTHrP) analogue with 41% homology to teriparatide and 76%
homology to PTHrP, is a selective activator of PTH receptor type 1

13. • The administration of abaloparatide over a period of 18 months
reduced the risks of new vertebral and nonvertebral fractures and
increased BMD at the hip, femoral neck, and lumbar spine in women
with postmenopausal osteoporosis when compared with placebo.
• Compared with patients treated with teriparatide, patients treated
with abaloparatide have been reported to have greater increases in
BMD and a lower frequency of hypercalcemia (3.4% versus 6.4%)

14. However, the overall rates of adverse
events, discontinuation due to
adverse events, and severe adverse
events have been reported to be
higher in association with
abaloparatide