Osteoporosis future therapies

1. Newer and future therapies for
osteoporosis

2. Current FDA-approved pharmacologic
options
• Bisphosphonates (alendronate, ibandronate, risedronate and
zoledronic acid)
• Estrogens (estrogen and/or hormone therapy)
• Estrogen agonist/antagonist (raloxifene)(December 9, 1997)
• Calcitonin (August 12, 2005)
• Parathyroid hormone (teriparatide) (November 26, 2002)
• RANKL inhibitor denosumab (June 1, 2010)
• Tissue-selective estrogen complex (conjugated
estrogens/bazedoxifene) (October 3, 2013)

3. Efficacy of current treatment regimens
( Bisphosphonates)
• Alendronate ↓ vertebral # and hip # by about 50 percent
over three years in patients with a prior vertebral fracture or
in patients who have osteoporosis at the hip site.
• It reduces the incidence of vertebral fractures by 48 percent
over three years in patients without a prior vertebral fracture.
• Ibandronate ↓ vertebral # by about 50 % over 3 years.
• Reduction in risk of nonvertebral fracture not documented.
Black DM et al. Lancet. 1996;348
Cummings et al, JAMA.1998

4. • Risedronate ↓ vertebral # by 41 to 49 %and non-vertebral #
by 36 % over three years, with significant risk reduction
occurring within one year of treatment in patients with a
prior vertebral fracture.
• Zoledronic acid ↓ vertebral # 70 percent (with significant
reduction at one year), hip # by 41 % and non-vertebral # by
25 percent.
Eastell R, Osteoporos Int. 2000
Efficacy of current treatment regimens
( Bisphosphonates)
Black et al, HORIZON PFT, NEJM May, 2007

5. Teriparatide
• Data from 8 randomised controlled trials – (n= 2388) to
evaluate the efficacy of daily subcutaneous teriparatide
injection in postmenopausal osteoporosis.
• Increase of bone mass of 8.14% (n = 2206) in spine and 2.48%
(n = 1303) at the hip.
• 70% risk reduction in vertebral fractures (three trials, n=
1452) and 38% risk reduction in non- vertebral fractures (risk
ratio 0.62)
• Caused an increase in the incidence of osteosarcoma in rats-
caution in conditions where osteosarcoma risk+.
Review by SL Han, IJCP, Jan 2012

6. Calcitonin
• Salmon calcitonin is FDA-approved for the treatment of
osteoporosis in women who are at least five years
postmenopausal when alternative treatments are not
suitable.
• Calcitonin ↓ vertebral # about 30 percent in those with prior
vertebral fractures but has not been shown to reduce the risk
of non-vertebral fractures.
Chesnut CH, PROOF Study Group. Am J Med. 2000

7. Raloxifene
• vertebral # ↓ by about 30 % in pts with H/o vertebral#.
• 55 % in patients without a prior vertebral # over three years.
• Reduction in risk of nonvertebral not documented.
• Raloxifene is also indicated for the reduction in risk of
invasive breast cancer in postmenopausal women with
osteoporosis.
• Raloxifene does not reduce the risk of coronary heart disease.
• DVT risk increased similar to estrogen.
Ettinger B. et al. JAMA. 1999

8. Summary of current treatment
regimens
Dose Interval Route BMD H % BMD S% #H % # S% A/E
Alendronate 70 mg Weekly Oral - - 50 48 ONJ,STF Femur
Risedronate 35 mg Weekly Oral - 9.3 36 49 Esophgitis
Ibandronate 150 mg Monthly Oral - 6.6 - 50 A/C Phase rn
Zoledronate 5mg Yearly IV 6.02 6.71 41 70 ↓Ca, Renal Dysfn
Raloxifene 60 mg Daily Oral 2.8 2.1 30,55 Thromboemboism
Teriparatide 20 mcg Daily SC 8.14 2.14 70 38 ↑ Ca, Diarea,Vom
Strontium 2g Daily Oral 9.8 - 36 39 TE,Skin rash,AbdD

9. Need for newer agents
• All bisphosphonates can affect renal function and are
contraindicated in patients with estimated GFR below30-35
ml/min.
• Zoledronic acid CI for Cr Cl< 35 mL/min
• ONJ
• Atypical femur fractures of bisphosphonates ( >5 years of
use).
• Cost of Teriparatide.

10. Bone Remodelling

11. Molecular mediators of remodelling

12. Points where intervention can be
made- Antiresorptive
The Lancet 2011

13. Points where intervention can be
made- Anabolic
The Lancet 2011

14. Newer agents
Antiresorptive agents:
•Denozumab
•Cathepsin k inhibitors
•Osteoprotegerin
•C-src kinase inhibitors
•Αvβ3 integrin antagonists
•Chloride channel inhibitors
•Nitrates.
Anabolic agents:
•Calcilytics
•Antibodies against sclerostin and
Dickkopf-1 (PC)
•Statins (Ob)
•Matrix extracellular
phosphoglycoprotein fragments
activin inhibitiors
•Endo-cannabinoid agonists
•Misc agents- Phytoestrogens,
Once a week PTH

15. Denozumab
• Denosumab, a human monoclonal antibody that specifically
binds RANKL blocks the binding of RANKL to RANK thereby
reducing bone resorption and increasing bone density.
• Subcutaneous injection every 6 months.
• Denosumab 60 mg- FDA approved for osteoporosis.
• Also approved in Europe for treatment of bone loss
associated with hormone ablation in men.

16. Comparison with alendronate-DECIDE study
• 1,189 postmenopausal women with low bone mineral density
(T score ≤−2.0 at the lumbar spine or total hip)
• Randomly assigned to denosumab 60 mg S/c for 6 months or
to oral alendronate 70 mg once weekly.
• At the end of 1 year, there was a significant increase in BMD
at the
– total hip (3.5 versus 2.6%),
– femoral neck (2.4 versus 1.8 %),
– lumbar spine (5.3 versus 4.2 %)
in denosumab group when compared to that of alendronate
(p<0.0001 at all sites).
Brown JP et al. J B M R 2009

17. STAND trial
• In 504 postmenopausal women (aged >55 years) with low
BMD (T score between −2.0 and −4.0) who were on
alendronate were randomly assigned to switch to denosumab
60 mg subcutaneously once every 6 months or to continue
alendronate 70 mg once weekly.
• At the end of 1 year, there was a small but significant increase
in BMD in denosumab cohort when compared to that of
alendronate group (1.9 % increase in total hip versus 1.0 %,
lumbar spine 3.0 versus 1.8 % increase) (p<0.0001).
Kendler DL, J B M R 2010

18. Denozumab-Comparison with
placebo- FREEDOM
• 7,868 PM osteoporosis women (60 to 90 years of age).
• Randomly assigned to subcutaneous denosumab (60 mg every
6 months) or placebo for 3 years.
• Denosumab increased lumbar spine BMD and total hip BMD
compared to that of placebo (9.2 versus 0 % and 4.0 versus
−2.0 %, respectively)
• Significantly ↓ the risk of new vertebral # by 68 % (P<0.001),
hip # by 40 % (P=0.04), and non-vertebral # by 20 %.
• Denosumab group had a lower rate of new vertebral fractures
(cumulative incidence 2.3 versus 7.2 %, relative risk 0.32 (95 %
CI 0.26–0.41)), a lower rate of hip (0.7 versus 1.2 %) and non-
vertebral (6.5 versus 8.5 %) fractures.
Cummings SR et al Denosumab for preventionof fractures in
postmenopausal women with osteoporosis. N E J M 361

19. FREEDOM extension trial
• FREEDOM denosumab group was continued on three more
years of denosumab for a total of 6 years and women from
the FREEDOM placebo group were given 3 years of
denosumab.
• Lumbar spine and hip BMD increased significantly at the end
of 6 years (15.2 and 7.2 %, respectively).
• In the crossover group, lumbar spine and total hip BMD
increased by 9.4 and 4.8 %, respectively.
HG Bone et al J. Clin. Endocrinol. Metab. (2013

20. Denosumab-Effects on bone histology,
microarchitecture and mineralization
• Qualitative evaluation of iliac crest bone biopsies collected
after 2 and/or 3 years in the FREEDOM trial showed normal
trabecular and cortical microarchitecture and normal
mineralization.
• On histomorphometric analysis, the significant reduction in
bone formation and bone resorption and osteoclast number
were noted in denosumab cohort.
• No significant difference between the denosumab and
placebo groups was noted in terms of trabecular volume and
cortical width.

21. • In FREEDOM trial, at the end of 2 years.
– Denosumab cohort had lower cortical porosity (3.64
versus 4.58 %; p=0.011)
– higher cortical volumetric BMD (866 versus 851 mg/cm3;
p=0.018) compared to placebo.
• In the biopsies that were obtained from STAND trial
participants,
– 82% less bone resorption in denosumab cohort when
compared to alendronate group.
Denosumab-bone histology, microarchitecture
and mineralization

22. Anti-sclerostin antibodies
• Sclerostin -a protein produced by osteocytes in bone acts by
antagonizing the anabolic Wnt signaling system on
osteoblasts, thus leading to anti-anabolic effect on bone.
• The binding of Wnt proteins to the LRP5/6-Frizzled co-
receptor on the cell membrane of osteoblasts
• Regulate gene transcription that promotes osteoblastic bone
formation

23. Animal Studies on sclerostin inhibitors
• Animal models showed a significant improvement in BMD in
mice.
• In estrogen-deficient ovariectomized rats, antisclerostin
antibodies increased the osteoblasts and decreased
osteoclast surfaces thereby reversing the bone loss that is
caused by estrogen deficiency.

24. Sclerostin Ab preclinical
• Monkeys administered with antisclerostin antibodies for two
consecutive months had significant improvement of bone
formation markers (osteocalcin).
• No change in the bone resorption markers (CTX).
• Increase in bone mineral content (BMC) and BMD at the
femoral neck, radius, and tibia, with dose-dependent
increases in bone formation were noted.
• Beneficial effects on fracture healing were also noted.

25. Phase 1
• Compared with placebo, significant improvements in lumbar
spine BMD was noted (p<0.01).
• Injection site erythema, back pain, headache, arthralgia, and
dizziness -considered mild.
• Non-specific hepatitis one patient- recovered in a week.
Single-dose, placebo-controlled, randomized study of
AMG 785, a sclerostin monoclonal antibody. J Bone Miner
Res

26. Phase 2
• Efficacy and tolerability of romosozumab was evaluated in a
phase 2 randomized, placebo-controlled study in 419
postmenopausal women aged 55–85 years (mean age 67
years) with lumbar spine, total hip, or femoral neck T score up
to −2.0 and at least −3.5.
• The study subjects were randomized to one of nine groups,
receiving once monthly romosozumab subcutaneously (70
mg, 140 mg, 210 mg) or once monthly subcutaneous placebo,
thrice monthly romosozumab (140 mg, 210 mg) or thrice
monthly subcutaneous placebo, or an open-label active
comparator of either subcutaneous teriparatide 20 μg daily or
oral alendronate 70 mg once weekly.
McClung M (2012) Inhibition of sclerostin with AMG 785 in postmenopausal
women with low bone mineral density: phase 2 trial results. J Bone Miner Res

27. Phase 2..
• There was a significant increase in lumbar spine, total hip, and
femoral neck BMD at end of 12 months with all doses of
romosozumab when compared to that of placebo (p<0.005)
and teriparatide and alendronate (p<0.0001), and all doses
significantly increased serum P1NP and reduced serum CTX
from baseline as early as week 1.
• The greatest BMD increase was seen with once monthly
subcutaneous romosozumab 210 mg, with a reported
increase of 11.3 % at the lumbar spine and 4.1 % at the total
hip.
• Romosozumab was generally well tolerated except Mild Inj.
site reactions (12% vs 4%)

28. Phase 3
• Romosozumab was evaluated in a randomized placebo-
controlled trial over a period of 1 year in 419 postmenopausal
women aged 55–85 years with low BMD (T score in range
−2.0 to −3.5).
• Subjects were randomized to receive monthly romosozumab
at doses 70 mg, 140 mg, and 210 mg or every three monthly
doses of 140 mg and 210 mg or placebo or alendronate 70 mg
weekly or 20 μg teriparatide daily.

29. Phase 3..
• At the end of 12 months, there were 11.3, 4.1, and 7.1 %
increase in bone mineral density at lumbar spine with 210 mg
dose of romosozumab, alendronate, and teriparatide,
respectively (p<0.001%),while placebo arm experienced
decrease of BMD by 0.1 % (p<0.006).
• Similar positive results were noticed in total hip and femoral
neck BMDs (p<0.02).
• No significant difference in adverse events was noticed
between the study cohorts except for increased injection site
reactions in romosozumab arm.

30. Blosozumab
• Two randomized placebo-controlled phase 1 trials involving
healthy postmenopausal women.
• It was noted that there was a significant increase in the levels
of bone formation markers, and there was 3.41 and 7.71 %
increase in lumbar spine BMD with single dose and multiple
doses of blosozumab, respectively .
• Phase 2 study that involved 154 postmenopausal women with
baseline age of 65 years and baseline T score of −2.76.
• Subjects were randomized to receive blosozumab 180 mg or
270 mg or placebo every 2 weeks subcutaneously (SC),
blosozumab 180 mg every 4 weeks SC.
McColm et al Blosozumab, a humanized monoclonal antibody against sclerostin,
demonstrated anabolic effects on bone in postmenopausal women. JBMR 2012

31. • At the end of 52 weeks, there was 6.7, 8.4, 13.9, and 17.8 %
increase in lumbar spine BMD with doses of blosozumab 270
mg every 12 weeks, 180 mg every 4 weeks, 180 mg every 2
weeks, and 270 mg every 2 weeks, respectively.
• No difference in adverse events was noted among the groups
except increased injection site reactions in blosozumab
group.
Blosozumab

32. Cathepsin K inhibitors
• Cathepsin K is a protease expressed in osteoclasts.
• Cathepsin K degrades type 1 collagen in organic bone.
• Cathepsin K inhibitors (e.g., odanicatib) inhibit matrix
dissolution, decrease bone resorption, and thus improve BMD
in postmenopausal women.
• Several cathepsin K inhibitors have been developed, while the
development was blocked in one of them because of serious
side effects (scleroderma-like changes in the skin).

33. Odanicatib
• In phase 1 studies, it was determined that once-daily regimen
is almost equal in efficacy to once-weekly dosage regimen.
• Promising results were seen in phase 2 studies of odanicatib
that showed significant linear increase in BMD at the lumbar
spine (11.9 %), femoral neck (9.8 %), and total hip (8.5 %) in 5
years.
• During this time frame, bone resorption markers were well
maintained while bone formation markers showed a slight
reduction.
• No fracture data of odanicatib is published yet.
Stoch et. al. Pharmacol Ther 2009
Brixen K et al JCEM 2013

34. Odanacatib..
• Phase 3 randomized placebo-controlled trial with 214
postmenopausal women with osteoporosis, and subjects
were randomized to receive either odanicatib 50 mg or
placebo.
• At 1 year, lumbar spine BMD was increased by 3.5 % and
bone resorption marker CTX decreased (p<0.001).
• 24 months, femoral neck BMD and BMC significantlyincreased
in odanicatib group (p<0.001).
• Currently, the drug is being evaluated in phase 3 trial
involving more than 16,000 postmenopausal women in which
Eisman et al JBMR 2011

35. Tissue specific estrogen analogues
• Newer SERMs that are in various stages of drug development
include bazedoxifene, lasofoxifene, and arzoxifene.
• Effective in preventing bone loss, preserving bone strength,
and reducing total cholesterol levels without evidence of
endometrial stimulation and fewer incidences of hot flushes.

36. Bazedoxifine
• At 1 year, no cases of endometrial hyperplasia were identifi
ed in the BZA 20-mg/CE 0.45-mg group, while three cases
(1.1%) were confi rmed for the BZA 20-mg/CE 0.625-mg group
(95% one-sided confidence interval upper limit 4%).
• Both BZA/CE doses signifi cantly increased lumbar spine and
total hip BMD versus placebo ( p 0.001) and showed low
incidences of bleeding and breast tenderness, similar to
placebo and signifi cantly lower than for CE 0.45 mg/MPA 1.5
mg.
Mirkin S. CLIMACTERIC 2013

37. Effi cacy of tissue-selective estrogen complex of bazedoxifene/
conjugated estrogens for osteoporosis prevention in at-risk
postmenopausal women .
Lindsay R Fertil Steril 2009

38. Phytoestrogens
• Genistein- An isoflavone phytoestrogen which is
the main ingredient in the prescription “medical
food” product Fosteum® and generally regarded as
safe by the FDA.
• Genistein may benefit bone health in
postmenopausal women but more data are needed
to fully understand its effects on bone health and
fracture risk.

39. Statins
• Enhance bone morphogenetic protein-2 gene expression and
bone formation in vivo.
• Increase of osteoblast number and promotion of osteoblastic
differentiation, leading onto increased bone formation by
simvastatin has been seen in animal models.
• The beneficial effect of statins on bone formation has also
been depicted in clinical studies
• However, the dose required for enhancing bone formation is
much higher than that of hypolipidemic action.
• Thus, there is a need to develop potent and preferably bone-
specific statin-related molecules.
Echistatin, a potential new drug for
osteoporosis.." Endocrinology

40. Osteoprotegerin
• Decoy receptor for RANKL.
• Preclinical studies that low bone turnover induced by OPG
overexpression leads to increased bone mass with no
evidence for deleterious effects on bone material properties.
• In a phase 1 clinical trial, OPG markedly decreased the
resorption marker urinary N-terminal telopeptide NTx by 80%
by day 4 after a single dose.
• Antibodies to OPG after its use that may hinder its future use
as a treatment for osteoporosis.
Bekker PJ, JBMR 2001

41. C-src kinase inhibitors
• The non-receptor tyrosine kinase c-src is required for the
development of the osteoclast ruffled border, one of the final
stages in the maturation of osteoclasts.
• Functional sealing zone and resorptive surface.
• Preliminary studies with c-src kinase inhibitors show
inhibition of bone resorption in vitro.
• Saracatinib is a novel orally available competitive inhibitor of
Src kinase shown to inhibit bone resorption in vitro.
• A randomized, double-blind, placebo-controlled, multiple-
ascending-dose phase I trial of saracatinib showed that it
inhibited osteoclast mediated bone resorption in healthy men
without any significant adverse effects.
Hannon RA, JBMR 2010

42. αv β3 integrin antagonists
• αv β3 integrin receptor or vitronectin receptor is present on
the surface of osteoclasts and is required for the attachment
of osteoclasts with bone matrix proteins.
• L-000845704 is an orally acting non-peptide antagonist of αv
β3 integrin receptor on osteoclasts and causes inhibition of
bone resorption.
• In a phase 2 trial involving 227 women with post-menopausal
osteoporosis, L-000845704 significantly decreased bone
resorption markers by 40% and increased spine BMD by 3.5%
at a dose of 200 mg bid.
• Preliminary data from in vitro studies suggested that a
neutralizing antibody α β decreases osteoclast attachment
and therefore, bone resorption.
Murphy MJ JCEM 2005

43. Chloride channel inhibitors
• Passive movement of chloride through chloride channel
(ClCN7) located in the cell membrane of the osteoclast is
required for secretion of acid from osteoclasts.
• In vitro studies have shown that ClCN7 inhibitors decrease
osteoclast acidification and inhibit the formation of
resorption pits and inhibit bone resorption in
ovariectomized rats without inducing obvious toxicity.
• In vitro studies of osteoclasts from human patients with
inactivating ClCN7 mutations depict normal
osteoclastogenesis, but a 80-90% reduction in the bone-
resorbing activity of the cells.
Henrikson et al. Am J Pathol. 2004
Sorenson, American Society for Bone and Mineral Research 2006

44. Nitrates
• The role of nitric oxide (NO) in skeletal homeostasis has been
realized lately.
• Augmentation of osteoblast function and inhibition
ofosteoclast development and function by NO has been
depicted by in vitro studies.
• Low-dose isosorbide mononitrate acts as a NO donor and has
shown to decrease markers of bone resorption while
increasing the markers of bone formation in post-menopausal
women.
• Another pharmaco-epidemiological case-control study also
indicates less incidence of fractures in persons receiving
nitrates.
Jamal SA, JBMR, 2004
Rejnmark L, JBMR,2006

45. Calcilytics
• Calcium-sensing receptor antagonists (calcilytics) are a new
drug class of orally administered agents that stimulate
endogenous PTH release and have bone forming action.
• JTT-305/MK-5442 and SB-423557 are two calcilytics that were
shown to increase bone formation and prevent bone loss in
ovariectomised rats.
• ATF 936 and ronacaleret are still under clinical trials for the
establishment of their role in the treatment of osteoporosis.
Wilder L, JBMR 2008
Fitzpatrick LA, JBMR 2008

46. Dickkopf-1 (Dkk-1) inhibiton
• Negative regulator of the WNT signaling pathway that acts by
directly binding to LRP5 and LRP6.
• Blocking these receptors lead to inhibition of
osteoblastogenesis in various osteogenic cell lines.
• A human monoclonal antibody to Dkk-1 has been tested in
ovariectomised monkeys and found to stimulate bone
formation, suggesting promise as a skeletal anabolic agent.
• However, the performance of these antibodies in humans is
awaited.
Li X, JBMR 2011

47. Cannabinoid agonists
• Endocannabinoids and their receptors have been seen to be
involved in the regulation of osteoblast differentiation and
bone formation.
• Cannabinoid CB1/2 agonist CP 55,940 and cannabinoid (CB) 2
selective agonists HU 308 have shown stimulation and early
differentiation of bone marrow derived osteoblast precursors
and enhancement of bone nodule formation in osteoblast
cultures in vitro.
• Currently, their role in the treatment of osteoporosis ?

48. Matrix extracellular phosphoglycoprotein
(MEPE) fragments
• MEPE is highly expressed in differentiated osteoblasts and
osteocytes and acts as an endogenous inhibitor of bone
mineralization.
• Deletion of the MEPE gene in mice leads to an increase in the
number and activity of osteoblasts leading to increased bone
mass.
• But it has been seen that MEPE 242-264, a fragment of MEPE
stimulate new bone formation and fracture healing in
preclinical studies.
• Thus full-length MEPE and MEPE fragments derived from
proteolytic cleavage may exert opposite effects.

49. Other bisphosphonates (etidronate,
pamidronate, tiludronate)
• These medications vary chemically from alendronate,
ibandronate, risedronate and zoledronic acid but are in the
same drug class.
• At this time, none is approved for prevention or treatment of
osteoporosis.

50. PTH (1-84)
• This medication is approved in some countries in
Europe for treatment of osteoporosis in women.
• RCT-DB with 2532 postmenopausal women with low
bone mineral density at the hip or lumbar spine.
• 100 mcg of recombinant human PTH or placebo daily
by subcutaneous injection.
• All received calcium, 700 mg/d, and vitamin D3, 400
U/d.
• Relative risk to the # incidence observed in the
placebo group was 0.62 [CI, 0.37 to 1.04] [P = 0.07]).
Greenspan SL, Ann Intern Med. 2007

51. PTH 1-84..
• Mean bone mineral density increased at the spine by 6.9%
and at the hip by 2.1% but decreased at the forearm in the
PTH-treated group.
• Parathyroid hormone treatment increased the percentage of
participants with hypercalciuria, hypercalcemia, and nausea
by 24% (CI, 20% to 27%), 23% (CI, 21% to 26%), and 14% (CI,
11% to 16%), respectively, compared with placebo.
Greenspan SL, Ann Intern Med. 2007

52. Teriparatide Once-Weekly Efficacy Research
(TOWER) Trial for Examining the Reduction in New
Vertebral Fractures in Subjects with Primary
Osteoporosis and High Fracture Risk
• Randomized, multicenter, double-blind, placebo-controlled
trial conducted in Japan.
• Subjects were 578 Japanese patients between the ages of 65
and 95 yr who had prevalent vertebral fracture.
• Subjects were randomly assigned to receive once-weekly sc
injections of teriparatide (56.5 g) or placebo for 72 wk.
• The primary endpoint was the incidence of new vertebral
fracture.
Nakamura et al. JCEM , September 2012

53. TOWER..
• Once-weekly injections of teriparatide reduced the risk of
new vertebral fracture with a cumulative incidence of 3.1% in
the teriparatide group, compared with 14.5%
• Relative risk of 0.20 (95% confidence interval, 0.09 to 0.45).
• At 72 wk, teriparatide administration increased bone mineral
density by 6.4, 3.0, and 2.3% at the lumbar spine, the total
hip, and the femoral neck, respectively, compared with the
placebo (P0.01).
• Adverse events (AE) and the dropout rates by AE were more
frequently experienced in the teriparatide group, but AE were
generally mild and tolerable
Nakamura et al. JCEM , September 2012

54. Summary
• Present antiresorptive treatments are effective, but some are
limited by side-effects, concurrent comorbidities, and
inadequate long-term compliance.
• The number of available drugs will increase considerably in
the coming years.
• Many of the new drugs combine efficacy with convenient
administration.
• Odanacatib and saracatinib represent a distinct class of
antiresorptives that inhibit osteoclast activity rather than
impairing osteoclast viability.
• There is a great need for additional and affordable anabolic
treatments in situations of severe osteoporosis, extensive
bone loss, and impaired fracture healing.

55. Thank You..