Agents affecting mineral ion homeostasis and bone turnover

1. AGENTS AFFECTING
MINERAL ION
HOMEOSTASIS AND BONE
TURNOVER
Dr M.KARTHIGA

2. OVERVIEW
1. MINERAL ION HOMEOSTASIS
2. HORMONAL REGULATION
3. NON HORMONAL REGULATION
4. BONE METABOLISM
5. DISORDERS OF BONE AND TREATMENT
6. RECENT ADVANCES

4. CALCIUM

5. UPTAKE ,STORAGE AND
EXCRETION
• PTH
• Sodium
ions
• diuretics

6. PHOSPHATES
• ABSORPTION – MOSTLY PASSIVE in intestine
• Reg by glucocorticoids,estradiol
• RENAL TRANSPORT THROUGH NPT2B
Decreases of serum phosphate enhance the
biogenesis of vitamin D, which in turn upregulates
NPT2B expression.
• 90%freely filtered in glomerulus, 80% reabsorbed at
PCT

7. HORMONAL REGULATION
1. Parathyroid hormone
2. Calcitriol(1,25- dihydroxyvitamin D3 )
3. Fibroblast Growth Factor 23 (FGF 23)
4. Calcitonin

8. PARATHYROID HORMONE

9. • PTHR - GPCRs Gs, Gq, and G12/13
• putative PTHR, CPTH
• CPTH receptors - expressed on osteocytes

10. REGULATION OF SECRETION
• Changes in serum Ca 2+
Calciferol suppresses PTH GENE EXPRESSION
• Calcium sensing receptors
• GPCR
Gq • Gq-PLC-IP3-Ca2 +PKC
Gi
• Inc cAMP
• Dec PKA,

12. PARATHYROID HORMONE AND
ITS ANALOGUES
• single-polypeptide chain of 84 amino acids -N-terminal portion
of the peptide;
• Currently available PTH analogues
1. Teriparatide, [hPTH(1–34)]
2. Recombinant human PTH consisting of 84 amino acids
[rhPTH(1–84)]
3. Abaloparatide,, hPTHrP(1-34).

13. TERIPARATIDE Tmax PTH =30mins
Tmax Ca2+ =3-4 hrs
t1/2 – 1 hr (sc), 5 mins (iv)
Vd – 0.1L/kg
Excretion – renal
Non enzymatic clearance
Dose 20mcg OD s.c
1. Prevention and t/t of
post menopausal
osteoporosis
2. Men with primary and
hypogonodal
osteoporosis
ABALOPARATID
E
Tmax –30 mins
t1 /2 – 1.7 hrs
Proteolytic degradation
Dose – 50 mcg OD s.c
rhPTH(1-84) Tmax (Ca2+ = 10-12 hrs)
Vd -5.3 L
t1/2 – 3 hrs
Dose – 25mcg OD
1. Hypocalcemia refractory
to other t/t
2. RISK EVALUATION
AND MITIGATION
SERVICE

14. • ADVERSE EFFECTS:
• Hypercalcemia
• Osteosarcoma- NOT TO BE USED > 2 YRS
• Paraaesthesia,headache and nausea
• NEWER : LA –PTH
• N-terminal biologically active region of PTH linked to a
collagen-binding domain Inc. BMD in mice

15. FIBROBLAST GROWTH FACTOR
23
• Osteocytes and other bone cells, including osteoblasts, and
lining cells
• Dietary phosphorus load and to changes in serum phosphate
and 1,25-dihydroxyvitamin D
• FUNCTIONS :
1. Phosphate excretion Inhibiting Cotransporters NPT2A
and NPT2C
2. Suppression of active vitamin D production by kidneys
3. Suppresses intestinal phosphate absorption

16. • .
• KRN23, (BUROSUMAB) which binds FGF23 and inhibits its
activity, can increase Pi reabsorption and serum
concentrations of Pi and calcitriol in patients with X Linked
Hypophosphaetemia(Carpenter et al., 2014; Imel et al., 2015).
• DOSE – 0.8 mg/kg to a max 90 mg ,s.c
• A/E- Headache, inj site reaction, vomiting, pyrexia, extremity
pain, vitamin D decreased, back pain, tooth infection, restless
leg syndrome, dizziness, constipation, blood phosphorus
increased; hypersensitivity, hyperphosphatemia,
nephrocalcinosis.
• Soluble klotho when administered to mice increased serum
levels of FGF23 and reduced bone mineral content with a
concomitant increase in fracture incidence (Smith et al., 2012
• Ab to soluble klotho fragment Secondary
hyperparathyroidism or CKD-MBD.

18. VITAMIN D
• Hormone
• VDR, a nuclear receptor
• Vitamin D3 (cholecalciferol)
and vitamin D2
(ergocalciferol).
• vitamin D3> vitamin D2.
• longer t1/2 of vitamin D3 and
lower affinity of vitamin D2
metabolites for the vitamin
D–binding protein.
• The total concentration of
serum 25-hydroxyvitamin D
(D2 + D3).
• 7-dehydrocholesterol, which is
synthesized in the skin.
• Ergosterol, plants and fungi,
is the provitamin for
ergocalciferol (vitamin D2).
• sure to ultraviolet radiation.

19. • Absorbed from the small intestine req Bile
• intestinal bypass surgery or inflammation of the small
intestine; hepatic or biliary dysfunction- dec absorption
• Bound to vitamin D binding protein
• Excreted by bile
• T1/2 -20-30 hrs, longer time in fat.
• RDA- 400 IU/Day < 1 yr
• 600 iu/day > 1yr

20. METABOLISM
T ½ - 19 days
T 1/2- 3
days

21. FUNCTIONS
• Inc. absorption and retention of Ca2+ and phosphate
1. Inc absorption of Ca2+ and phosphate in the small intestine
2. Interacts with PTH to enhance their mobilization from bone
3. Dec their renal excretion. entry across mucosal membranes
mediated by TRPV6 and Ca(v)1.3 Ca2+ channels •
diffusion through the enterocytes • active extrusion
across serosal plasma membranes
• upregulates the synthesis of FGF23, calbindin-D9K,
calbindin-D28K, and the serosal plasma membrane Ca2+-
ATPase

22. Doxercalciferol (1α-hydroxyvitamin
D2
• Ergocalciferol (calciferol) - vitamin D2
• ORAL , 50,000–200,000 units/d
+calcium
• prevention of vitamin D deficiency
familial hypophosphatemia,
hypoparathyroidism
• vitamin D–resistant rickets type II,
• DHT - reduced form of vitamin
D2.
• DHT 25-OH dihydrotachysterol
(LIVER )
• mobilizing bone mineral at high
dosesmaintain plasma Ca2+ in
hypoparathyroidism.
• well absorbed from GI tract
• maximally increases serum Ca2+
concentration after 2 weeks of
daily administration
• effects typically persist for 2
weeks
• ORAL - 0.2 to 1 mg/d (average 0.6
mg/d).
• 1α-Hydroxycholecalciferol (1-OHD3,
alfacalcidol)
• synthetic vitamin D3 derivative
• rapidly hydroxylated by 25-
hydroxylase to form 1,25-(OH)2D3.
• stimulation of intestinal absorption of
Ca2+ and bone mineralization;
• U.S. - experimental purposes

23. CALCITRIOL ANALOGUES-
• suppress PTH secretion by the parathyroid glands
• less or negligible hypercalcemic activity
• Calcipotriene (Calcipotriol- Psoriasis
• Paricalcitol -(1,25-dihydroxy-19-norvitamin D2- secondary
hyperparathyroidism in patients with CKD
• Maxacalcitol. 1,25-dihydroxy-22-oxavitamin D3, OCT, and 22-
oxacalcitriol,
• low affinity for vitamin D–binding protein
• Rapid metabolism

24. NUTRITIONAL
RICKETS
INFANTS 400 U/Day
1000U/day – mild rickets
3000-4000U/day= severe
HYPOPARATHYROIDIS
M
• DHT, a reduced form of
vitamin D2,
• faster onset, shorter duration
of action, and greater effect
on bone mobilization
• calcitriol - preferred for
temporary treatment of
hypocalcemia
OSTEOPOROSIS.CKD MBD-OTHER USES

25. • osteocalcin, a vitamin K–dependent protein that contains γ-
carboxyglutamic acid residues,
• IL-1, a lymphokine that promotes bone resorption.
• Bone-mobilizing hormone but not a bone-forming hormone
OTHER USES
• Maturation and differentiation of mononuclear cells
• influences cytokine production and immune function.
• Inhibits epidermal proliferation, promotes epidermal
differentiation-plaque psoriasis

26. CALCITONIN
• Hypocalcemic hormone
• Opposes PTH
• Parafollicular cells of thyroid
gland
• Inhibits osteoclast mediated
bone resorption esp during
Calcium stress
• CTR, a GPCR that links to Gs
and Gq.
• Rx - Hypercalcemia,Pagets
disease
• Tumor marker of Medullary
Thyroid cancer
• circulating t1/2 of calcitonin is
about 10 min.

27. CALCITONIN
• CTR, a GPCR
• Direct inhibition of osteoclastic bone resorption
hypocalcemic and hypophosphatemic
• Secreted in response to serum Ca
• USE : Diagnosis of MTC
• Hypercalcemia i.v/nasal spray
• Pagets disease and osteoporosis – s.c ,100 units/day f/b
50units 3x a week
• A/E- nausea, hand swelling, urticaria, intestinal cramping.
Hypersensitivity reactions, including anaphylaxis,

28. • Salcatonin: synthetic salmon salmon calcitonin Synthetic
(recombinant) human calcitonin - s.c. or i.m. inj. or intranasal
(200 IU/day) administration
• plasma t1/2: 4-12 min, but action lasts for hours –
• Side effects: local inflammation at injection site, nausea,
vomiting, flush, unpleasant taste, tingling of the hands
• Clinical uses: hypercalcaemia, osteoporosis (vertebral
compressions

29. BONE
• BONE MASS –Bone Mineral Density
• Age- Major increases in bone mass, accounting for
about 60% of final adult levels, occur during
adolescence, mainly during years of highest growth
velocity
• circulating estrogen and androgens, physical
activity, and dietary calcium
• BONE REMODELLING – Continous Process of
Rebuiding and Resorption

30. • BONE MASS- Bone mineral mass
• Peaks during the third decade, remains stable until age 50,
and then declines progressively
• Regulating factors  Physical activity
• Circulating estrogens
Calcium in diet
BONE FORMATION AND REMODELLING

31. RANKL
• upregulation
• PTH, 1,25-dihydroxyvitamin
D (1,25-[OH]2-D) , Calcium .
Glucocorticoids ,
prostaglandin E2 ,inteleukin
(IL)-1α, IL-6, IL-11, and IL-17
• downregulation -
transforming growth factor
(TGF)-β
Osteoprotegyrin
• Inc OPG
• 1,25-(OH)2-D ,Calcium ,IL-1α,
IL-6, IL-11, IL-17, oestrogen –
TGF-β, bone morphogenetic
protein (BMP)-2,
• Dec OPG
• PTH , Glucocorticoids –
prostaglandin E2 , insulin-
like growth factor 1

32. DISORDERS OF MINERAL ION
HOMEOSTASIS AND BONE
METABOLISM
• HYPOCALCAEMIA
• HYPERCALCAEMIA
• OSTEOMALACIA
• HYPERPHOSPHATEMIA
• HYPERVITAMINOSIS D
• METABOLIC RICKETS
• OSTEOPOROSIS
• PAGETS DISEASE
• CKD MBD
CALCIUM
PHOSPHAT
E
VITAMIN D

33. HYPERCALCAEMIA
• Primary hyperparathyroidism,
• Malignancy with or without bony metastasis ( PTHrP )
• Vitamin D Excess
• Hyperthyroidism
• Immobilisation
• S/P Renal Transplantation d/t persistent hyperfunctioning
parathyroid tissue
• Serum PTH, PTHrP, and 25-OH- and 1,25-(OH)2D 
DIAGNOSIS

35. HYPOCALCEMIA
• Malabsorption state- Combined deprivation of Ca2+ , vitamin
D, phosphate, total plasma proteins,
• Pseudohypoparathyroidism - hypocalcemic and
hyperphosphatemic
• d/t resistance to PTH; this resistance is due to mutations in
Gsα (GNAS1), which normally mediates hormone-induced
adenylyl cyclase activation
• Hypoparathyroidism -thyroid or neck surgery ,genetic or
autoimmune disorders.
• Rx - CALCIUM

36. • Calcium carbonate and Calcium oxalate – oral
OTHER USES
• Magnesium toxicity 1g Calcium gluconate by slow iv push
• Black spider envenomation
• Hyperkalemia

37. HYPERPHOSPHATEMIA
• CKD High phosphates dec Ca 2+ Inc PTH
• Secondary Hyperparathyrodism  Hypercalcaemia
• CINACALCET CaSR agonist
HYPOPHOSPHATEMIA
• D/T Antacids
• KRN23 – FGF23 Antagonist XLH

38. CINACALCET
• TYPE II Calcimimetic
• CaSR modulators requiring Ca2+
• mimic the stimulatory effect of Ca2+ on the CaSR
• to inhibit PTH secretion by the parathyroid glands.
• ADME – BA – 20-25 % : C max after 2-6 hrs
• Maximal effects on serum PTH occur 2–4 h after
administration.
• Large Vd – 1000l
• metabolized CYPs 3A4, 2D6, and 1A2.
• Elimination - biliary (15%) and renal excretion (85%).
• t1/2 of 30–40 h.

39. USES ADVANTAGES ADVERSE EFFECTS
1)Secondary
hyperparathyroidism in
adults with CKD on
dialysis ( 30mg OD)
(2) Hypercalcemia in
adults with parathyroid
carcinoma; (30 mg BD)
(3) hypercalcemia with
primary
hyperparathyroidism
candidates for surgical
parathyroidectomy.
1. Reduced renal
functions
2. Dec FGF23
3. Dec bone turnover
1. HYPOCALCAEMIA
2. Seizure threshold dec
1. PTH <150 pg/ml
Adynamic bone disease
8.4mg/dl
DRUG INTERACTIONS
Dose adjustments
1. CYP3A4 Inhibitors (e.g., ketoconazole,
erythromycin, or itraconazole).
2. CYP2D6 substrates - flecainide, vinblastine, and
most tricyclic antidepressants

40. RICKETS
1) Hypophosphatemic vitamin D–
resistant rickets:
X-linked disorder (XLH) of
calcium and phosphate
metabolism.
2) Vitamin D–dependent
rickets/VDDR-1 or PDDR:
• AR, mutations in CYP1α (1α-
hydroxylase)
• defective conversion of 25-OHD
to calcitriol
3) vitamin D–dependent rickets
type II:
• AR, heterogeneous mutations
of the VDR
• hypocalcemia, osteomalacia,
rickets, and total alopecia.
variant.
4)
• CKD-MBD (renal rickets):
abnormalities of bone turnover,
mineralization, volume, linear
growth, or strength, as well as
underlying defects in mineral
ion, PTH, or vitamin D
metabolism.

41. • HYPERVITAMINOSIS D
• RX
• immediate withdrawal of the vitamin, a low-calcium diet,
administration of glucocorticoids, and vigorous fluid support;
forced saline diuresis with loop diuretics is also useful. With
this regimen, the plasma Ca2+ concentration falls to normal,
and Ca2+ in soft tissue tends to be mobilized.

42. Oestrogens:
• Maintaining bone integrity (during repr. cycle in women)
• inhibit cytokines that recruit Ocs - diminish bone-resorbing
action of PTH
Glucocorticoids: - physiological concentrations are required for
OB differentiation
• excessive concentrations (pharmacological or pathological)
inhibit OB differentiation and activity + stimulate OC
action osteoporosis
Thyroid hormones: - Osteoid formation - OB activity

43. HORMONE –LIKE SUBSTANCES
• Raloxifen (selective oestrogen
receptor modulator: SERM):
• advantage over HRT: induce
agonistic actions on some
• systems (bone and CV system)
and antagonistic on others
• (mammary glands and uterus)
• - D-dependent increase in OB
activity (IGF-I) and reduction in
OC action (IL-6, IL-1, TNF↓)
• - Increasing bone density and
decreasing pathological risks (45-
50%)
• -good GI absorption, extensive
first-pass metabolism (BA:
• 2%), wide distribution, fecal
excretion,
• plasma t1/2: 32 h
• - Side effects: hot flushes, leg
cramps, venous
• thrombembolism (?

44. BISPHOSPHONATES

46. • ORAL/IV
• BA –LOW,
• Extensive distribution in bone
• excreted unchnged by
kidneys not recommended
Cr CL<30ML/Min
• USES
• Paget disease, tumor-
associated osteolysis
• osteoporosis
• breast cancer - endocrine
adjuvant therapy
• ADVERSE EFFECTS
• GI Effects- heartburn,
esophageal irritation, or
esophagitis
• Skin flushing, flu-like
symptoms, muscle and joint
aches and pains, nausea and
vomiting, abdominal
• Osteonecrosis of the jaw
• Stress fractures in the lateral
cortex of the femoral shaft
• Zoledronate – Renal toxicity

47. ETIDRONATE ORAL,IV Iv – Pagets disease-5mg/kg/day
TILUDRONAT
E
ORAL 400 mg x 3 months
PAMIDRONAT
E
IV 60–90 mg over 2–24 h.
hypercalcemia associated with malignancy & Paget
disease
prevention of bone loss in breast cancer and multiple
myeloma;
ALENDRONA
TE
ORAL 10 mg OD x 1 week Osteonecrosis of jaw
IBANDRONAT
E
ORAL,IV 1. 3mg i.v every 3 months
Less GI effects
2. Postmenopausal osteoporosis- 2.5 mg daily or 150
mg one evry 3 months
ZOLEDRONAT
E
IV 1. Pagets – 5mg iv single infusion every 6 months
2. Hypercalcemia of malignancy, multiple myeloma, or
bone metastasis resulting from solid tumors- 4mg
3. Osteoporosis – 5mg yearly
RISENDRONA
TE
ORAL 5mg OD for osteoporosis
30mg/day – Pagets disease

48. OSTEOPOROSIS
• Low bone mass and microarchitectural disruption
• Fractures with minimal trauma
• -women (30%–50%) and men (15%–30%)
• vertebral bodies, the distal radius, and the proximal femur,
ribs and long bones also are common.
PRIMARY OSTEOPOROSIS SECONDARY OSTEOPOROSIS
1. TYPE 1 - loss of trabecular bone
owing to estrogen lack at
menopause
2. TYPE 2 -loss of cortical and
trabecular bone in men and women
due to
a)long-term remodeling inefficiency
b)dietary inadequacy
c) activation of the parathyroid axis
with age
1. Systemic illness
2. Drugs – Glucocorticoids,Phenytoin,

49. MANAGEMENT
ANTI
RESORPTIVE
•BISPHOSPHONA
TES
•DENOSUMAB
•VITAMIN D
•CALCITONIN
•CALCIUM
•SERMS
•ESTROGEN
ANABOLIC
•TERIPARATIDE
•ABALOPARATID
E
COMBINED
•Alendronate
+Raloxifen
•Risedronate+Terip
aratide

50. BISPHOSPHONATES FIRST LINE drugs
Alendronate, risedronate, and
ibandronate – t/t Glucocorticoid induce
DENOSUMAB
1. MAb
2. Binds to RANKL and mimics
Osteoproteogyrin
3. Inhibits osteoclast maturation and
resorption
4. RANKL
60 mg once every 6 months, s.c
Osteonecrosis of jaw
C.I. in hypocalcemic
Other uses
Bony mets, GCT
SELECTIVE ESTROGEN RECEPTOR
MODULATORS
RALOXIFEN
1. D-dependent increase in OB activity
(IGF-I)
2. reduction in OC action (IL-6, IL-1,
TNF↓)
3. induce agonistic actions (bone and
liver) and antagonistic on (mammary
glands
1. Increasing bone density (2-3% per
year) and decreasing pathological
risks (45-50%)
2. good GI absorption, extensive first-
pass metabolism (BA: 2%), wide
distribution, fecal excretion, plasma
t1/2: 32 h –
3. Side effects: hot flushes, leg cramps,
venous thrombembolism

51. VITAMIN D
1. improve intestinal Ca2+
absorption,
2. suppress bone remodeling,
CALCITRIOL
1. suppress parathyroid function
directly
2. reduce bone turnover.
• 400–800 IU/d- improve BMD in
individuals with marginal or
deficient vitamin D status
• Restriction of dietary calcium
may reduce toxicity during
calcitriol therapy
CALCITONIN
1. Direct inhibition of osteoclastic
resorption
• Dose - s.c. or i.m. inj. or
intranasal (200 IU/day)
• plasma t1/2: 4-12 min, but
action lasts for hours –
• Side effects: local inflammation
at injection site, nausea,
vomiting, flush, unpleasant
taste, tingling of the hands
TERIPARATiDE
increases predominantly
trabecular bone at the lumbar
spine and femoral neck;.
20-mcg dose, OD..S/C
adverse effects
injection-site pain, nausea,
headaches, leg cramps, and
dizziness

52. CALCIUM
Elderly, preteen and adolescents
1000- 1300 mg /day
Calcium Carbonate
STRONTIUM RANEOLATE-
WITHDRAWN
1. Dual action
2. Stimulates ob to produce
Osteoprotegyrin
3. Stimulates CaSROsteoblastic
1. BA -5%
2. Protein binding 25% for
plasma protein and high
affinity for bone tissue
3. not metabolised.
4. Elimination half-life 60 hours
5. Excretion Renal and
gastrointestinal.
6. Plasma clearance is about 12
ml/min (CV 22%) and renal
clearance about 7 ml/min (CV
28%)
7. venous thromboembolism,
pulmonary embolism and
serious cardiovascular
disorders

53. REVISED GUIDELINES 2018
• AMERICAN COLLEGE OF PHYSICIANS
1. Alendronate, risedronate, zoledronic acid, and denosumab,
which have been shown to reduce vertebral, nonvertebral,
and hip fractures, should be offered to women with
osteoporosis to help decrease their risk of experiencing a hip
or vertebral fracture.
2. Calcium and vitamin D can be added as dietary
supplements

54. 3. Pharmacologic treatment should continue for five years in
these women
4. Hormone therapy with estrogen or estrogen/progestogen, or
raloxifene should not be used to treat women with osteoporosis.
5. >65 yrs t/t based on should take into account patient
preference, fracture risk, benefits, harms, and costs
6. Use of PTH analogues not more than 2 yrs

55. PAGETS DISEASE
• Single or multiple sites of disordered bone remodeling
• >60 years of age.
• increased bone resorption F/B exuberant bone formation
Disorganised newly formed bone,
bowing, stress fractures, and arthritis of joints
Malignant degeneration to osteogenic sarcoma - complication

56. TREATMENT
• Bisphosphonates and calcitonin.
• An initial course of bisphosphonate typically is given once
daily or once weekly for 6 months.
• . Intravenous pamidronate , Zoledronate
• . Compared with calcitonin, bisphosphonates have the
advantage of oral administration, lower cost, lack of
antigenicity, and generally

57. CHRONIC KIDNEY DIESEASE-
MINERAL BONE DISEASE
1. Decreased Ca +2 reabsorption
2. Secondary hyperparathyroidism
3. Hyperphosphataemia
4. Dec production of calcitriol
5. Inc FGF 23
INCREASED BONE
METABOLISM
UNDERMINERALIZATION
OF BONE

58. MANAGEMENT
DIETARY
PHOSPHATE
RESTRICTION
PHOSPHATE
BINDERS
Ca BASED
NON Ca BASED
CALCITRIOL

59. PHOSPHATE BINDERS
SEVALEMER
HYDROCHLORIDE
SEVALEMER CARBONATE
nonabsorbable polymer -nonselective anion
exchanger..
1. Dec serum phosphate concentration in
hemodialysis patients
2. binds bile acids,low-density lipoprotein
cholesterol and fat-soluble vitamins.
3. A/E : vomitting, nausea, diarrhea, dyspepsia,
and metabolic acidosis
LANTHANUM CARBONATE Poorly permeable trivalent cation
C/I – Bowel obstruction
SUCROFERRIC
OXYHYDROXIDE
(oral)
polynuclear iron(III)–oxyhydroxide
1. by ligand exchange.
2. lower daily pill burden.
FERRIC CITRATE Improves hematopoetic parameters
Diarrhoea

60. RECENT ADVANCES
• Transdermal patch of abaloparatide
• Etecalcetide – Calcimimmetic ,for hyperparathyroidism
• ronacaleret -Inhibits CaSR (calcilytics) stimulate the secretion
of PTH and decrease renal excretion of Ca2+

61. • Romosuzumab –Humanised Mab against sclerostin- IND
• Finding of sclerostin to low-density lipoprotein receptor-
related proteins 5 and 6 (LRP5 and LRP6) prevents activation
of canonical Wnt signaling in bone, resulting in decreased
bone formation

62. • The Fracture Study in Postmenopausal Women with
Osteoporosis (FRAME)
• Active-Controlled Fracture Study in Postmenopausal Women
with Osteoporosis at High Risk (ARCH
• BLOSUZUMAB - inhibits SOST, a negative regulator of
osteoblast activity
• Ipriflavone (INN, JAN; brand name Yambolap) is
a synthetic isoflavone which may be used to inhibit bone
resorption,[2] maintain bone density and to
prevent osteoporosis in postmenopausal women. Only in
Japan
• ODANACATIB – Cathepsin k Inhibitor ,inhibits bone