24. PHARMACOLOGY OF BONE METABOLISM. PHARMACOTHERAPY OF OSTEOPOROSIS.

Type of drug Drug Administration/PK Indications: You should know Adverse effects
Calcium salts and CHOLECALCIFEROL Oral: powders, Osteoporosis: Intestine: ↑ Ca abs Constipation
vitamin D (needs hydroxylation tablets.. -As monotherapy: doubtful efficacy Osteoblasts: improves Flatulence
-As adjuvant in treatments ↑ CV risk
Calcium: 1000- in kidney) After meals and bone formation
-combined w/ fixed Hypocalcemia Nephrolithiasis
1200mg/day fractioning dose Hypoparathyroidism Parathyroid: ↓ PTH
dose of Ca Hypercalcemia
Vit D: 400- (500mg/dose) Osteomalacia Bone: activates
CALCIFEROL Weakness
800UI/day Lack of vit D osteoclasts to release Ca
CALCITRIOL Nausea, v
Polyuria, polydipsia
Calcitriol: risk
hypercalcemia, monitor!
ANTIRESORPTIVE
DRUGS (↓ bone
loss)
Bisphosphonates Analogues of Resistant to metabolism Of choice: 1º & 2º osteoporosis Remove after 3-5 years GI: ulcers &
pyrophosphate: role in of phosphatases of treatment in ppl w/o esophagitis
regulating bone -Oral on empty
resorption high risk of fractures. Bone pain
stomach. Abs Atypical femoral
impaired by fractures.
food(low bio.) Osteonecrosis of the
-Standing position jaw
-20-80%: bone
mineralization sites
R-enal excretion
Non nitrogenated Simple compounds They are incorporated Accumulate inside osteoclasts 
similar to into ATP analogues  apoptosis
pyrophosphate
1st generation ETIDRONATE oral 1º, 2º osteoporosis.
Reduces vertebral fractures
Nitrogenated More potent. Ability to Inhibit mevalonate No mb anchoring  osteoclast cant
chelate divalent cations. pathway  attach to bone
High affinity for bone
2nd generation ALENDRONATE Oral, weekly 1º, 2º osteoporosis.
Reduces vertebral and hip
fractures
RISENDRONATE Oral. 1º, 2º osteoporosis.
Weekly/monthly Reduces vertebral and hip
fractures
-Paget’s disease
IBANDRONATE Oral monthly 1º, 2º osteoporosis.
i.v. quarterly Reduces vertebral fractures
-bone malignancies, breast
cancer metastatic to bone
3rd generation ZOLENDRONATE i.v. quarterly 1º, 2º osteoporosis. In bone cancer Osteonecrosis of the
hospital use only Reduces vertebral and hip hypercalcemia jaw. Not frequent
fractures
-Paget’s disease
-bone malignancy (1/year)
Denusomab DENOSUMAB Reversibly 1.Osteoporosis (post- 2nd line drug Osteonecrosis of the
(RANK inhibitor) Recombinant hm inhibition of menopause). ↓ risk of vertebral jaw (rarely)
AB (IgG2) that inh. resorption and non vertebral fractures Hypocalcemia
RANKL (mimic OPG) 2.Bone loss due to hormonal Altered bowel habit:
ablation (prostate cancer). d/c
3.Prevention of skeleton related Dyspnea
events in bone metastases. Risk atypical femur
fractures
Estrogenic ESTRADIOL or + Oral/percutaneous osteoporosis prevention in PMW Dual action: N, v. headaches,
analogues (HRT) PROGESTEOGENS who cannot tolerate others ↓ resorption: supress stress, breast tender.
PMW w/ estrogen deficiency genes that codify RANKL Mood changes
Surgical post-menopause and IL-6 ↑ venous TE
↑ osteoblast activity ↑ breast, ovarian cancer
 contraindications
Estrogen-dependent
cancer
Pregnancy
Severe liver disease
Venous/pulmonary TE
SERMs. Selective RALOXIFENE Agonist: bone and ↓ breast cancer risk ↓resorption ↑ risk of venous and
estrogen receptor BAZEDOXIFENE CV system (ER-B) Systemic effect: ↓ total ↑ bone mineral density pulmonary TE
modulators Antagonists: cholesterol and LDL ↓osteoclast activity CONTRAINDICATIONS
breast, uterus (ERa) ↑ osteoblast activity
Treatment & prevention Pregnancy
ORAL. 1/day w/o osteoporosis in PMW Venous TE history
food 3rd line: alternatie to Hepatic/renal disease
bisphosphonates & desonumab
Calcitonin SALCATONIN s.c./ i.m. injection Prevention of acute bone loss ↓resorption: reversibly Inflammation after inj
(synthetic salmon short treatment: 2- due to immobilization inhibits osteoclast GI: N,V
calcitonin) 4 weeks activity Vascular: facial flush
Synthetic human Calcium 4h after Paget’s disease (don’t respond to Tingling in hands
CALCITONIN adm: 500mg others/contraindicated). Cancer (prolonged
treatments)
Cancer related hypercalcemia CONTRAINDICATED
-Allergy to fish protein
- Hypocalcemia
ANABOLIC DRUGS
(bone formation)
Parathyroid PTH Daily s.c. injection Treatment osteoporosis in PMW Continuous adm: Transient
hormone & TERIPATIDE Max: 24 months Glucocorticoid 2º osteoporosis catabolic effect. hypercalcemia
teripatide Treatment of severe Paradox: small doses + N, d, h
osteoporosis (others fail) osteoblast and enhace Leg cramps
bone formation CONTRAINDICATIONS
Hipercalcemia
 Reversible effect  Hyperparathyroidism
bisphosphonates after Bone radiotherapy
Paget’s disease
Severe renal ins.
OTHER DRUGS STRONTIUM RESTRICTED: severe osteoporosis ↓resorption NOT IN
RANELATE and ↑ risk of fractures. Don’t ↑ osteoblast activity UNCONTROLLED
respond to others & no CV history HYPERTENSION.
Hospital diagnosis drug. Altered consciousness,
seizures
Hepatitis
Severe skin reactions
VTE, MI