Management of Osteoporosis

DEXA report analysis

• Postmenopausal women / Men age > 50 with T score
less than – 2.5 : Treat
• Postmenopausal women / Men age > 50 with T score –
1 to 2.5, use FRAX, if predicted 10 year risk for hip
fracture as > 3 % or any major osteoporotic fracture as
> 20 % : Treat
• Premenopausal women, men < 50 with Z score less
than – 2.0 : Search for secondary causes, treatment
decision individualized
NOF: Age < 50 / Premenopausal women
Candidates for pharmacotherapy
 Pre menopausal women - minimal risk of
fractures and lack of large RCTs
 Premenopausal osteoporosis is often a result
of an underlying condition or medication
 Treatment of primary cause
 NOF: Candidates for pharmacotherapy
 Postmenopausal women (and men ≥50 years)
with a history of hip or vertebral fracture
 Postmenopausal women (and men ≥50 years)
with osteoporosis based upon BMD
measurement (T-score ≤-2.5)
 If Osteopenia, FRAX score suggestive of 10-
year probability of hip fracture 3 % or more /
10-year probability of major osteoporotic
fractures combined 20 % or more
Essential workup prior to OP therapy
 Serum Calcium / Corrected Calcium
level
 Alkaline phosphatase and inorg.
Phosphorus level
 S. Creatinine
 CBC
 Vit D level
 OP management plan

 Therapeutic options
 Choosing treatment option
 Monitoring OP therapy
 Precautions while on therapy
 Duration of therapy
 Options to prevent Osteoporosis

 Calcium 1200 mg (diet plus supplements)

 Vitamin D 800 – 2000 IU
 Physical exercise
 Attainment of good peak bone mass
Primary OP : management
 Options to treat Osteoporosis

 Oral / IV Bisphosphonates
 Denosumab
 Anabolic agents : Teriparatide , Abaloparatide
 Raloxifene
 Others : E+P, Calcitriol, Calcitonin, Vit K2,
Strontium ranelate ,Tibolone, Isoflavones,
 Management of OP
 Document normal serum Calcium & Vit D
 Oral Bisphosphonates is 1st line therapy
 If Oral Bisphosphonates contraindicated, IV
Bisphosphonates
 Other options - Denosumab , Teriparatide
 Teriparatide as initial therapy if T-score of - 3.5
or below or T-score of - 2.5 or below plus a
fragility fracture
Bisphosphonates
 Bisphosphonates
 Structural similarity to native pyrophosphate
 Common P-C-P structure, like P-O-P structure
of native bone mineral
 Bone mineralization
 Hydroxyapatite is deposited in the extracellular
matrix : Mineralization
 Inorganic pyrophosphate circulare in blood and
inhibits hydroxyapatite formation and thus
mineralization
 Alkaline phosphatase hydrolyzes
pyrophosphate and promote mineralization
 Bisphosphonates : Mechanism
 Bisphosphanates are pyrophosphate analogs,
reach in bone and attach to hydroxyapatite
 Osteoclast resorb bone hydroxyapatite
impregnated with bisphosphonates
 Impair ability of bone resorption by osteoclast
 Promote osteoclast apoptosis
 Reduce bone resorption as well as bone
formation
 Bisphosphonates : Pharmacology
 Primarily Inhibit bone resorption
 1 – 5 % of oral dose absorbed
 Best absorption on empty stomach
 No food or medication for next 30 – 60 minutes
 70% cleared by kidney
 30% taken up by bone
 Indicated in all conditions associated with
excess bone resorption
 Bisphosphonates
 Oral : Alendronate 70 mg per week ,
Risedronate 35 mg per week , Ibandronate
150 mg per month
 Injectable : Zolendronic acid 5mg every year ,
Ibandronate 3mg every 3 monthly
 Bisphosphonates : Risks
 Oral preparations: Reflux, esophagitis , ulcer
 IV Zolendronic acid : flu like syndrome for 24 to
72 hours
 Both IV and oral : Hypocalcemia ,
Osteonecrosis of jaw , atypical femur fracture
(Treatment of osteoporosis with bisphosphonates for up
to five years is not associated with atypical fractures )
 Bisphosphonates: Duration of
therapy in Postmenopausal OP
 Oral : 5 Years
 IV 3 years
 Oral for 10 year and IV for 6 years if women at
highest risk for fracture (history of osteoporotic
fracture before or during therapy, T-score below -3.5
in the absence of fractures
 If fracture during therapy : stop and reinitiate
bisphosphonates four to six weeks post fracture
 Restart : if persistent bone loss > 5% in 3 years
Contraindications:Bisphosphonates

 Esophageal disorders
 Inability to follow dosing requirements
 Post R Y Gastric by pass surgery
 Estimated GFR < 30
Denosumab
 Denosumab in OP

 Human monoclonal antibody that specifically

binds RANKL on Osteoblast
 Blocks the binding of RANKL to RANK
 Reduces the formation, function, and survival
of osteoclasts
 Decreased bone resorption and increased
bone density
RANKL(on Osteoblast) and RANK
 Denosumab indications & dose
 OP with impaired renal function (<30 e GFR)
 Intolerance to Bisphosphonates
 Dose 60 mg administered by subcutaneous
injection once every six months
 Administered in upper arm, thigh, or abdomen
 No dose adjustments for chronic kidney
disease
 Duration of therapy : indefinite
PTH analog
 Bone and PTH : Contradiction

 PTH causes bone resorption

 PTH used as Bone formation stimulating
agent in treatment of OP
 PTH Replacement
 Net bone loss (resorption) when
administered in a continuous fashion
 Net bone formation (deposition) when
administered intermittently
 Using PTH in OP
• BMD decreased in Hyperparathyroidism
• Osteoblast express PTH receptor
• Stimulation of Osteoblast : bone remodeling
• PTH : Chronic elevation – Bone resorption
• PTH : Intermittent elevation – Bone formation
 PTH dose in OP

 Teriparatide : 20 mcg SC
 Abaloparatide : 80 mcg SC
 Duration of therapy : maximum 2 years
 S. Calcium monitoring : sample to be drawn
after at least 24 hours after last dose
 Monotoring therpay in OP

 DEXA at 2 year interval

 P1NP (Serum N-terminal propeptide of type 1
procollagen ) measurement
 P 1 NP level measurement
• To be measured before beginning of OP therapy and 3 to 6
month later
• Normal range : 20 – 90 mcg/L
• The direction of the change depend on the type of
osteoporosis treatment
• Bisphosphonates : Reduction of > 20 % from base line after
6 months of therapy indicate good response
• Teriparatide : Increase of > 10 mcg/L indicate good
response
Secondary OP : management
 Management of Glucocorticoid OP
 Increase bone resorption by suppressing osteoprotegerin,
stimulating RANK, decrease intestinal calcium absorption,
inhibit osteoblast proliferation
 Evaluate all patients by DEXA who need steroid therapy for > 3
months
 For age > 50 / postmenopausal women : all with high risk to be
treated
 For age < 50 / premenopausal women : need of treatment to
be individualized ( therapy to be considered for patients on
high dose steroid)
 Bisphosphanates are first line therapy
 Consideration for Teriparatide : if contraindication to
bisphosphanates / severe cases
 Management of OP with CKD
 If eGFR > 30 + No evidence of MBD : treat OP as
usual
 If eGFR < 30 + MBD : manage secondary
hyperparathyroidism , OP not to be treated
 If eGFR < 30 & absence of MBD : Consider
Denosumab ( Off label use of Bisphosphonates with
half dose if no option )
 Use of Teriparatide restricted to biopsy proven
adynamic bone disease
 Osteoporosis: Conclusions
 Screening by DEXA to diagnose
 Calcium / phosphate / Alk phos should be
normal in primary OP
 OP can be secondary and need etiology based
management
 Bisphosphanates : 1st line therapy for Pri. OP
 Vit D adequecy is essential in OP
 Teriparatide / Denosumab are to be used in
selective patients