osteoporosis

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Pharmacy
Current updates and new horizon
in osteoporosis management
Emad Elbanna (MD)
Assistant professor of orthopaedic surgery
Beni Suef University

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Definition
1. Osteoporosis is a progressive systemic skeletal
disease characterised by low bone mass and micro-
architectural deterioration of bone tissue with a
consequent increase in bone fragility and
susceptibility to fracture.
2. .

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• Trabecular bone is more susceptible to the effects of
osteoporosis
• Most osteoporotic fractures occur where there are
high levels of trabecular bone eg the vertebrae, the
neck of femur (hip) and the wrist

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Bone tissue cells
Basically three :
• Osteoclasts- large multi-nuclear cells which release
enzymes and acids that digest protein and mineral components
of bone (resorption)
• Osteoblasts- bone builders, synthesize and secrete collagen
and other components to create a matrix which is laid down in
the bone. They initiate calcification of the matrix and hence bone
formation
• Osteocytes- mature bone cells (osteoblasts encased in
matrix secretions) responsible for exchange of waste and
nutrients.

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Pathophysiology
• Bone is constantly re-modelled and repaired due to
damage caused by daily use
• Osteoclasts “cut” into old bone (resorption) and
osteoblasts fill with organic matrix which becomes
mineralised (bone formation or ossification)
• In osteoporosis the net rate of bone resorption
exceed rate of bone formation- normally matched.
• Results in a decrease in bone mass and quality

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-Cathepsin K :very potent protease secreted by the
activated osteoclast
Resulting in degradation of bone matrix and
breakdown of mineral component of bone tissue.
-Oxidative stress in bone :Imbalance between
production of reactive oxygen species (ROS) and
antioxidant
Resulting in decreased bone mass
formation,osteoblast formation,number and
dysfunction

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• One in 3 women and one in 12 men over 50 will
sustain an osteoporotic fracture in their lifetime

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Risk factors for Osteoporosis
• Age
• Premature menopause or hysterectomy
Gender
•
Genetic factors
Smoking –Alcohol
Obesity
Low Vitamin D and calcium level

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Secondary causes of
osteoporosis
• Long term corticosteroid use ie 5mg or more prednisolone daily for 3
months or more
• Aromatase inhibitor treatment
• Hyperparathyroidism
• Hyperthyroidism
• Coeliac disease, malabsorption syndromes, inflammatory bowel
disease,IBS
• Anorexia
• Renal disease
• Rheumatoid arthritis
• Other drugs- PPI’S, SSRI’s, Anti-epileptics

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-Asymptomatic disease
-Generalized bony pain
-Fragility fractures (vertebrae,rib,hip and wrist)
Diagnosis of osteoporosis

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DEXA scan
DEXA is the most popular method for measurig Bone Mineral
Density(BMD)
Osteoporosis is diagnosed when BMD is less than or equal to 2.5
standard deviation below that of young age (30-40 years old)

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Management
-The aim of treatment is to prevent fractures
-Non pharmacological measures
-Pharmacological agents

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Pharmacological agents
Traditional drugs
-Antiresorptive measures:
Bisphsphanate
Estrogen agonists
Calcitonin
Denosumab
-Anabolic agents:
Teriparatide

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-Cathepsin K inhibitor (Odanacatib)
-Anti-sclerostin antibodies (Romozumab)
-Regulating activin signaling (under research)
-Insulin like growth factor 1 (under research)
New agents

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Vitamin K
Folic acid
Vitamin B12 supplementations
Androgen
Fluoride
Cytokines and cytokine antagonists (under
research)
Other therapies

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The aim of combintion is synergistic and additive
antiresorptive effect
Combined agents of different mechanisms as
antiresorptive and anabolic agents like combination of
Bisphosphonate and Teriparatide
Combined agents of the same mechanisms as
combination of Bisphosphonate and Estrogen
Combination of anti-inflamatory agents (anti TNF) with
anti sclerostin antibodies
Combination therapy

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Bisphosphonates
• First line treatment
• inhibit action of osteoclasts
• Available as daily, weekly and monthly oral preparations and 3
monthly and yearly injections
• Daily and weekly- alendronate, risedronate, etidronate
• Monthly- ibandronate
• 3 monthly IV- ibandronate infusion
• Yearly IV- zoledronate infusion

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Bisphosphonates cont.
-Oral bisphosphonates have complicated dosage regimes and poor
bioavailability
-Strong evidence to support their use
-Accumulates in skeleton
-Alendronate usually first choice due to cost
-GI Side effects are fairly common with oral bisphosphonates
-Recent concerns regarding osteonecrosis of the jaw especially
with high dose intravenous versions
-Increased risk of low trauma atypical subtrochanteric fracture
femur
-

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Strontium
• Reduce bone resorption and increas bone formation by its action on
osteoclasts and osteoblasts
• Available as a powder for reconstitution and taken daily usually bedtime
• Avoidance of food required 2 hours before and after administration
• GIT side effects of nausea and diarrhoea but usually transient
• Possible slight increase in risk of venous thromboembolism (VTE)
• Possibility of DRESS syndrome occurring (rare)

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• Raloxifene- selective oestrogen receptor modulator (SERM) which
selectively binds to oestrogen receptors on bone.
• Reduces incidence of vertebral fractures but no effect on non-
vertebral or hip fractures. Carries risk of VTE. Not for
postmenopausal women for primary prevention.
• Teriparatide- a fragment of recombinant human parathyroid
hormone. High levels of parathyroid hormone usually cause bone
resorption but pulsed doses cause formation. Daily injection.
Reduces vertebral and non-vertebral fractures but not hip.
Expensive and usually initiated by specialists.

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Calcium and Vitamin D3 - has an important role on bone formation and
remodelling. Calcium is required for bone mineralization and vitamin D keeps
parathyroid hormone secretion under control (esp elderly & housebound)
• Consider using alone or in combination with biphosphonates
Calcitonin- hormone produced by thyroid gland. Given as a nasal
spray of synthetic calcitonin. Reduces risk of vertebral fracture only

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The first biological agent
Inhbits RANKL
Administrated every 6 months S.C
Not cleared by the kidney
Possible increased adherence to rgimen
But impact immune system infection
Marked suppression of bone remodeling
Long term safety and efficacy unknown
Denosumab

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Oral bioavalability
Weekly administration
do not accumulate in skeletal tissues
good effect on mineral density
Biopsy suggest bone safety
Cathepsin K

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Emerging drug
Inhibits sclerostin which secreted by osteoclast to reduce
bone formation by interfering with proliferation and function of
osteoblast
FDA has rejected approval of Romosuzamb due to high rate
of serious cardiovascular complication(july 2017)
Other antibodies developed and tested as Blosozumab
Antisclerosin antibodies

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-Enhance the differntaited function of the osteoclast and
bone formation
-Parenteral administration
-High adverse effects
-Lack of tissue specificity
-Possible role in some malignancies
All these factors are concern for development of IGF1 as
a theapeutic agent for osteoporosis
Insulin like growth factor

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More studies needed to be conducted for understanding :
-signaling pathway
-Prevention of osteoporosis
-Safety and efficacy of pharmacological agents
-Drug discovery
-Antioxidative measurement
Recommendations for future research

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