This ppt discusses advances in osteoporosis and the role of teriparatide in its management.

1. Advances in use of
TERIPARATIDE !!!
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OSTEOPOROSIS SERIES

2. Osteoporosis
• “Silent disease” until complicated by
fractures
• Most common bone disease in humans
• Characterized by:
– Low bone mass
– Microarchitectural deterioration
– Compromised bone strength
– Increased risk for fracture
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3. World Health Organization
Diagnostic Criteria
DIAGNOSIS BMD CRITERIA*
• Normal within 1 SD of a “young normal”
adult (T-score at -1.0 and above)
• Osteopenia between 1 and 2.5 SD below
that of a “young normal” adult
(T-score between -1 and -2.5)
• Osteoporosis 2.5 SD or more below that of a “young
normal” adult (T-score at or below -2.5)
• Severe Osteoporosis 2.5 SD or more below that of a “young normal”
adult and fracture(s)
• T-score is the number of SDs above or below the average BMD value for young,
normal adults of the same sex
BMD = Bone mineral density SD = Standard deviation
*Measured at the hip, spine, or wrist
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4. FRAX®
• Statistically robust fracture risk prediction
tool developed by the WHO for world-wide
use
• Combines BMD + clinical risk factors to
predict fracture risk better than either
alone
• Predicts the 10-year probability of major
osteoporotic fractureHip, spine, wrist, or
humerus.Use when the decision to treat is
uncertain
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RISK FACTORS
• History of fracture as an adult
• Fragility fracture in first degree relative
• Caucasian/Asian postmenopausal woman
• Low body weight (< 127 lb)
• Current smoking
• Use of oral corticosteroids > 3 mo.
• Calcium intake
• Physical activity/strength
• But the least bothered by all is,,,,,

6. Considered as poison
throughout the world !!!
That is
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7. SALT
High salt intake,,,,,
Risk factor for renal excretion
of calcium.
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8. Universal Recommendations
• Adequate intake of calcium, vitamin D
• Weight-bearing and muscle-strengthening exercises
to reduce risk of falls/fracture
• Provide strategies for fall prevention
• Avoidance of tobacco use/excessive alcohol use
• Have a bone density test and take medication when
appropriate
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9. Calcium/Vitamin D
• Adequate intakes of dietary calcium
and vitamin D, including
supplements if necessary
• Elemental calcium per day (> 50 YOA) =
at least 1200 -1500 mg
• Vitamin D3 per day (> 50 YOA) = 800 -
1000 international units (IU)
• Vitamin D3 (cholecalciferol) plays
major role in Ca absorption
• Inexpensive, well-tolerated
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10. Who Should Be Treated?
• Initiate therapy to reduce fractures in
postmenopausal women/men > 50
with:
1. BMD T-scores < -2.5 at hip or spine
2. Prior vertebral or hip fracture
3. Low bone mass (T-scores -1.0 to -2.5 at
hip or spine)
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11. FDA-Approved Drugs for Osteoporosis
• Bisphosphonates- alendronate, risedronate
• Selective Estrogen Receptor
Modulators (SERMs)- raloxifene
• Calcitonin, Estrogen/Hormone
Therapy (ET/HT)
• Parathyroid Hormone-
Teriparatide
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12. Antiresorptive Agents
• Estrogen
• Calcitonin
• Bisphosphonates
• SERMs (selective estrogen receptor
modulators)
• Anti-RANK ligand antibody (in Development)
• Cathepsin K inhibitors (in Development)
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13. Why do you need
TERIPARATIDE ?
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14. Treatment of Osteoporosis: Unmet Needs
and Emerging Solutions.( J Bone Metab. 2018
Aug;25(3)
• Efficient therapies are available for
the treatment of osteoporosis,
however, there are still unmet
needs. Anti-resorptive therapies only
increase bone mineral density to a
certain extent and reduce the risk of
non-vertebral fractures by 20%.
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15. Parathyroid Hormone
[PTH (1-34)] Teriparatide
Anabolic agent
• Mechanism: recombinant formulation of endogenous
parathyroid hormone (PTH) .
– stimulates osteoblast function, increases
gastrointestinal calcium absorption,
increases renal tubular reabsorption of
calcium
– Enhances bone turnover by initiating
greater bone formation
– Abaloparatide-under development
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16. 8/7/2019 PSPatki 16
TERIPARATIDE STRUCTURE

17. Teriparatide: rhPTH [1-34]
• The only treatment agent that is anabolic—
stimulates bone formation rather than inhibiting
bone resorption 20 μg daily (subcutaneously) for no
more than 2 years, The patents will expire in the
United States and in Europe in August 2019.
• Indication: treatment of men and postmenopausal
women with osteoporosis who are at high risk for
fracture
• Effects-
– Increased bone density in spine by 9% and hip by
3% vs placebo over 18 months
– Reduced incidence of vertebral fractures (65%) and
nonvertebral fragility fractures (53%) in women with
pre-existing vertebral fractures.
– Adverse reactions: arthralgia, pain, nausea; warning
about osteosarcoma risk in rats8/7/2019 PSPatki 17

18. Mechanism of action
• Teriparatide is a portion of human parathyroid
hormone (PTH), amino acid sequence 1 through 34,
of the complete molecule (containing 84 amino
acids). Endogenous PTH is the primary regulator of
calcium and phosphate metabolism in bone and
kidney. PTH increases serum calcium, partially
accomplishing this by increasing bone resorption.
Intermittent exposure to PTH will activate
osteoblasts . Thus, once-daily injections of
teriparatide have a net effect of stimulating new
bone formation leading to increased bone mineral
density.
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CD- CALLUS DIFF

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Based upon the difference in kinetics of changes between bone
formation and bone resorption markers, an "anabolic window"
is formed during which the actions of parathyroid hormone are
seen. believed to be maximally anabolic

21. Mechanism of Fracture
Risk Reduction
Anabolic therapy
Stabilize or improve
microarchitecture
Increase bone turnover
Decrease in fracture risk
Increase BMD
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22. What is the advantage ?
• Unlike anti-resportive agents which stop high
bone turnover, teriparatide creates
new bone tissue.
• Osteoanabolic hormone for bone formation.
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23. Clinical Efficacy
• Shown to decrease the risk of
new vertebral fractures by 65%
and nonvertebral fractures by
53% versus placebo after
median exposure of 19 months
• Increases lumbar spine BMD as
well as at the femoral neck,
total hip, and total body
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24. Effect of Teriparatide on Risk of
Vertebral Fractures in
Postmenopausal Women
0
2
4
6
8
10
12
14
16
Placebo Teriparatide 20
µg
%ofPatientswith≥1Fracture
RR 0.35 (95% CI = 0.22–0.55)
a
65% 
a
P <.001 vs placebo.
Neer RM, et al. N Engl J Med. 2001;344:1434-1441.
Graphic courtesy of Dr. Paul Miller.
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25. Effects of teriparatide and risedronate on new
fractures in post-menopausal women with severe
osteoporosis (VERO): a multicentre, double-blind,
double-dummy, randomised controlled trial
LANCET. VOLUME 391, ISSUE 10117, P230-
240, JANUARY 20, 2018
• Among post-menopausal women
with severe osteoporosis, the
risk of new vertebral and
clinical fractures is significantly
lower in patients receiving
teriparatide than in those
receiving risedronate. (680
patients in each group.)
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26. PTH (1-34)
Place in Therapy:
• Recommend PTH for women or men with severe
osteoporosis (low bone mineral density [T-score < -
2.5] and at least one fragility fracture) who are
refractory to or unable to tolerate bisphosphonate
therapy
• It is also occasionally used off-label to speed
fracture healing.
• In patients considered to be bisphosphonate
"failures," PTH may be started approximately 3
months after bisphosphonates are discontinued
• Antiresorptive therapy may be considered after
discontinuation of PTH to maintain gains in BMD
acquired with PTH alone in those at high risk for
subsequent fracture8/7/2019 PSPatki 26

27. teraparatide
• Teriparatide is the only anabolic (i.e., bone
growing) agent indicated for use in postmenopausal
women with osteoporosis at a high risk for fracture
or with a history of osteoporotic fracture, patients
with multiple risk factors for fracture, and for
patients who have failed or are intolerant to other
available osteoporosis therapy. It has been FDA-
approved since 2002. It is effective in growing bone
(e.g., 8% increase in bone density in the spine after
one year) and reducing the risk of fragility
fractures. Osteoporosis medications are generally
safe, but some side effects of teriparatide include
headache, nausea, dizziness, and limb pain.
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28. Osteoporos Int. 2018 Aug 13. 4658-7. [Epub ahead of
print]
The effects of teriparatide on acceleration of bone
healing following atypical femoral fracture:
comparison between daily and weekly administration.
• When all patents were included, the fracture healing time
was not significantly different between the two groups.
Only patients with complete AFFs had significantly fewer
daily bisphosphonate or denosumab injections than the
weekly group . The fracture healing time in the daily
group was significantly shorter than that in the weekly
group (P < 0.05). Even if the influence of bisphosphonate
or denosumab usage was excluded, a similar significant
difference was observed in the fracture healing time
(P < 0.05). There was no significant difference between
the two groups among patients with incomplete AFFs.
• CONCLUSIONS:Daily teriparatide injections enhance
bone union more than weekly injections in complete AFF
patients.
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29. Bone. 2018 Nov;116:58-66. 2018.07.013. 2018 Jul 18.
Real-world effectiveness of teriparatide on fracture
reduction in patients with osteoporosis and
comorbidities or risk factors for fractures: Integrated
analysis of 4 prospective observational studies.
• Data from 4 real-world observational
studies showed statistically significant
reductions during teriparatide treatment in
rates of CVF, NVF, and clinical fractures in
clinically relevant patient subgroups.
These results should be interpreted in the
context of the non-controlled design of the
source studies.
• CVF-CLINICAL VERTEBRAL FRACTURES, NVF- NON
VERTEBRAL.
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30. BALTIMORE STUDY, 2018
Effect of an intensive conservative therapy
with daily teriparatide administration and
rehabilitation for osteoporotic delayed
vertebral collapse and paralysis.
• Eventually 12 out of 30 patients avoided
surgical treatment because their
symptoms were improved. The results that
40% of patients with osteoporotic delayed
vertebral collapse (ODVC) did not need
further surgical treatment after the
intensive conservative treatment was of
great significance. Patients with greater
mobility of collapsed vertebrae might be
treated surgically as quickly as possible.
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31. Arch Osteoporos. 2018 May 2;13(1):50. doi: 10.1007/s11657-
018-0444-6.
Long-term benefits and risks of parathyroid hormone
treatment in compliant osteoporotic patients. A Danish
national register based cohort study.
• PTH treatment is effective and safe.
Following PTH treatment in compliant
patients, neither fracture incidence nor
drug consumption differed between PTH-
treated and BP-treated patients, despite
the fact that PTH-treated patients had
more severe osteoporosis. No increased
incidence of malignant diseases or other
diseases was detected.
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32. Teriparatide
• Use 20 mcg/d by sc injection
• Contraindicated in :
Hypercalcemia
Hyperparathyroidism
Unexplained elevated ALP
Exposure to external beam radiation
or prior
skeletal radiation8/7/2019 PSPatki 32

33. FDA Label Contraindications
to Teriparatide
• Unexplained hypercalcemia
• Unexplained elevated alkaline phosphatase
• Paget’s disease
• Prior skeletal (therapeutic) radiation
• Metastatic cancer
• Unfused epiphysis
• GFR <30 mL/min
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Differences between Anabolics: Teriparatide and
Romosozumab
•
Teriparatide is an amino acid terminal fragment 1‐34 of par
athyroid hormone – Stimulates osteoblastic and osteoclastic
activity
Promotes the formation of new bone by increased remodeling •
Romosozumab
is a monoclonal antibody that binds sclerostin, an osteocyte‐derive
d inhibitor of bone formation – Stimulates osteoblastic
activity and reduces osteoclastic activity –
Promotes the formation of new bone and decreases bone resorption

35. Support THE BONE
They support you !!!
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drpatki@gmail.com

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