Osteoporosis Management

Dr R M Maboa
BSc. MBCHB. DOMH
(Diploma in Occupational Health & Medicine)
11 February 2020

MBCHB IV

Sefako Makgatho Health Science University

Department of Pharmacology and Therapeutics

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 Overview
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 Classification of Osteoporotic treatment

 Indications
 Prevention of Osteoporosis
 Pharmacotherapy of Osteoporosis
 Biphosphanates:-
 Mechanism of actions
 Indications
 Pharmacokinetics
 Adverse effects
 Drug interactions

 Strontium ranelate
 SERMs

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 What is Osteoporosis?

• World Health Organization (WHO) definition: bone density of

2.5 standard deviation below the young healthy adult mean
value

• Bone mineral density, fracture

risk in post menopausal women
and older men

• Morbidity

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 A. Bone Remodeling
» ~10% of skeleton is replaced annually
• Removes damaged bone and replace bone to maintain calcium homeostasis
↓
Osteoclasts: cells that breakdown bone= Bone resorption
↓
Osteoblasts: synthesize new bone
↓
Hydroxyapatite deposited in new bone matrix (Bone mineralization)=Bone
strength
↓
Bone loss= bone resorption>bone formation during this process

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Osteoporosis

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 B. Prevention of Osteoporosis
• Calcium 800mg -1gram daily po (if lack of dietary intake)
• Calcium carbonate to be taken with meals
• Calcium citrate =+/- food
• Adverse effects: gas and bloating
• May interfere with iron preps absorption
• , thyroid replacement, fluroquinolones, tetracyclines
• Vitamin D 400-800 IU all life, daily intake
• Absorption of calcium is important and bone health
• Vitamin D2 , D3 used as treatment
• Symptomatic treatment
• Muscle relaxants
• Bed rest
• Physiotherapy
• Severe pain: Pamidronate IV
• Weight bearing exercises
• Avoid smoking and excessive alcohol intake -↓BMD-↑fracture risk
• HRT

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 Aim of Osteoporosis
• Prevent loss
• Improve bone strength
• Reduce risk of fracture

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 Pharmacotherapy of Osteoporosis
• Calcium, vitamin D, oestrogen,
• selective oestrogen receptor modulators-Raloxifene
• Biphosphonates
• Calcitonin
• Teriparatide-stimulators of bone formation
• Strontium ranelate- drugs with dual or complex actions on bone
• Hormone Replacement Therapy (HRT)- premature menopause

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 Biphosphonates
• Drugs:
• Alendronic acid*
• Clodronic acid
• Ibandronic acid
• Oral bisphosphonates
• Pamidronic acid-IV – moderate Paget’s disease
• Risedronic acid* – Severe hypercalcemia
• Zoledronic acid*-IV • Osteonecrosis of jaw(CA)-
* First line therapy:-
dentist
• postmenopausal osteoporosis
• Male osteoporosis • Complication chronic use:
• Glucocorticoid induced osteoporosis Atypical fragility fractures-
review Tx in 5 years
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 MOA-Biphosphonates

• Decrease osteoclastic bone resorption mainly through an increase in

osteoclastic apoptosis(programmed cell death)

↓
• Inhibition of the cholesterol biosynthetic pathway

↓
• Results in small increase in bone mass

↓
• Decrease risk of fractures in osteoporotic patients

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 Indications

• Osteoporosis fracture
• BMD T score ≤-2.5
• Osteogenesis imperfecta
• Prophylaxis and treatment of
female osteoporosis

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 Pharmacokinetics-Biphosphonates
• A: oral administration is poor,
food and other drugs interfere
with absorption
• D: distributed widely throughout
the body – primarily in bone, but
also in soft tissues such as the
liver, kidney and spleen
• M: not metabolized
• E: kidney-unchanged in urine

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 Drug Interactions

• Antacids
• Calcium containing products
• NSAIDS e,g Ibuprofen
• Aspirin

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 Contraindications Biphosphonates
• Hypocalcemia
• osteomalacia
• Renal impairment: creat<35ml/min
• GIT: esophageal
disorders/emptying, gastritis,
duodenitis,
• Inability to stand or sit up for at
least 30 mins
• Pregnancy
• Lactation
• Children <18years

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 Medications –Postmenopausal women
CLASSIFICATIONS Biphosphonates Selective oestrogen Anti-parathyroid Parathyroid hormone Other –bone
receptor metabolism
modulators(SERM)

MOA • ↓osteoclastic • Binds to • ↓ bone • Stimulate osteoblasts

bone estrogen resorption bone formation
resorption receptors • ↑renal • Bone resorption
• Inhibition • Inhibits bone excretion of stimulation
cholestrol resorption calcium
biosynthetic
pathway
Adverse Effects Diarrhoea, Abd Hot flashes, leg Rhinitis Headache, nausea, leg
pain, esophagitis, cramps, risk of cramps,↑CA, UA, Calciuria
esophageal venous
ulcers, headache throboembolism
Drug Alendronic acid Raloxifene Calcitonin Teriparatide Strontium
Ibandronic acid Cinacalcet ranelate
Zoledronic acid
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 Why do you use Parathyroid preparations to treat
Osteoporosis?
• Parathyroid hormone
• Increases the amount of calcium in circulation
• Promotes calcium absorption in the intestines
• Slows the excretion by the kidneys
• Stimulate bone formation and bone loss(too much PTH accelerates bone loss,
low doses of PTH can increase bone mass and strengthen bone
• Number of osteoblasts increases

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 Strontium ranelate

• Severe osteoporosis in postmenopausal women

• Men at high risk of fracture
• Failed treatment with other agents
• A Dual action to generate more osteoblasts and decrease the number of osteoclasts

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 Strontium ranelate
Drug Interactions Adverse Effects

• Calcium-containing agents • N/D/headache, dermatitis,

• Antacids eczema
• Tetracyclines
• Quinolones • Venous thromboembolism
• DRESS-drug induced rash
with eosinophilia and
systemic symptoms
* take 2 hours apart

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 Selective oestrogen receptor modulators (SERM)
• Oestrogen replacement is essential for the prevention of postmenpausal bone loss
• Mechanism of action: Binds to estrogen receptors, inhibits bone resorption
• Drugs: Raloxifene
– prevention and treatment of osteoporosis. It has oestrogenm-like effects
on bone and oestrogen antagonists effects on breat and endometrial
tissue
– It increases bone density without increasing the risk of endometrial
cancer
– Decreases the risk of invasive breast cancer
• It should be used an alternative to biphosphonates as there is no evidence to
suggest that decreases hip fractures

• Adverse Effects: hot flashes, leg cramps, increases of venous thromboembolism

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Biphosphonates and SERM

Mechanism of Action
Pharmacokinetics
Contra-indications
Drug Interactions
Adverse Effects

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