Treatment of Osteoporosis




  • Used for osteoporosis treatment.


  • Due to their inhibitory effect on osteoclast-mediated bone resorption.
  • Two mechanisms –
    • By accelerating osteoclastic apoptosis.
    • By suppressing differentiation of osteoclast precursors to mature osteoclasts – By IL-6 inhibition.
  • Reduces cholesterol synthesis via farnesyl pyrophosphate synthase inhibition, by bisphosphonates.


  • 1st generation agents:
    • Medronate, clodronate & etidronate
    • Least potent.
  • 2nd generation agents:
    • Alendronate, ibadronate & pamidronate.
    • Half-life of alendronate in bone – 10 years.
    • Long-term use can cause serious adverse effects.
  • 3rd generation agents:
    • Risedronate & zoledronate.
    • Most potent.
    • Zoledronate infusion of 5mg once yearly.


  • Treatment of post-menopausal & steroid-induced osteoporosis.
  • Paget’s disease.
  • Hypercalcemia of malignancy – Mainly pamidronate & zoledronate, by i.v route preferred.
  • Malignancies.
    • Eg: Zoledronate – As an adjunct in treating Philadelphia-chromosome positive CML.


  • Renal dysfunction
  • Esophageal motility disorders
  • Peptic ulcer.

Adverse effects:

  • Esophageal irritation resulting in ulceration – Distinctive toxicity.
    • Prevented by not taking drug by mouth & not to lie down at least for half an hour.
    • Minimizes chances of drug touching esophagus.
  • Causes hypocalcemia & also, hypercalcemia.
  • 1st generation bisphosphonate – Result in osteomalacia.
  • Zoledronate – Renal toxicity & osteonecrosis of jaw.

Long-term use:

  • Increases risk of atypical ‘chalkstick’ fracture of femur (subtrochanteric or shaft).
    • On concurrent high dose steroid therapy, risk is doubled.
  • Increases risk of esophageal cancer.



  • Estrogens inhibit bone resorption – 
    • Directly by inhibiting osteoclasts
    • Indirectly by modulating paracrine factors.
  • Increases anti-resorptive [IGF-1 & TGF-β].
  • Suppresses pro-resorptive [IL-1, IL-6, TNF-α, and osteocalcin] factor synthesis by osteoblasts.
  • Increases bone formation.


  • In Postmenopausal osteoporosis:
    • Estrogen deficiency in old age results in postmenopausal osteoporosis.
    • Use of hormone replacement therapy predisposes patients to adverse effects of estrogens, on breast & endometrium (increased incidence of breast & endometrial carcinoma).

Important drugs:

1. Raloxifene:

  • Exhibits estrogen agonistic action on bone & antagonistic action on breast & endometrium.
  • Hence preferred drug for treatment & prevention of post-menopausal osteoporosis.
  • Adverse effect: Increased risk of thromboembolism (Major).

2. Bazedoxifene:

  • Recently approved SERM for prevention of postmenopausal osteoporosis.
  • Also treats vasomotor symptoms of menopause.


  • A recombinant PTH1-34.
  • Intermittent s.c. administration.
  • PTH actions:
    • PTH in low & pulsatile dose – Stimulates bone formation.
    • PTH in excess – Causes bone resorption.


  • Teriparatide & strontium ranelate stimulates osteoblast.
  • (Most osteoporotic drugs act by inhibiting osteoclast).

Drug effects:

  • Stimulates new collagenous bone.
  • Mineralization of newly formed collagenous bone is essential.
  • Hence, sufficient vitamin D intake & calcium is advised.

Dosage & effects:

  • On administering 20 mcg/d subcutaneously for 2 years – 
    • Teriparatide dramatically improves bone density in most bones, except distal radius.
    • Recommended dose not to be exceeded.
  • Teriparatide course –-> followed by –> bisphosphonates course – Considered for retaining & improving bone density.


  • For healing of chalk stick fractures associated with bisphosphonate therapy.

Adverse effects & contraindications:

  • Potential risk of osteosarcoma, on very high doses.
    • Hence, C/I in:
    • Paget’s disease of bone
    • Prior radiotherapy to bone
    • Past history of osteo or chondrosarcoma
  • Unexplained increase in alkaline phosphatase
  • Patient’s on corticosteroids & thiazide diuretics.
  • Oral calcium supplementation advised (due to hypercalcemic risk).

Other adverse effects:

  • Exacerbation of nephrolithiasis.
  • Elevation of serum uric acid levels.


  • A monoclonal antibody against RANK ligand, useful for osteoporosis treatment.


  • Osteoclasts express receptor named ‘receptor for activated nuclear factor κ B (RANK), on its surface.
  • On receptor stimulation, by RANK ligand–> bone resorption occurs.
  • Due to osteoclasts activation.


  • Osteoprotegerin acts as a decoy receptor for RANK ligand.
  • MOA: 
    • Binds it, preventing RANK-L binding to osteoclasts.
  • Uses:
    • Prevents osteoporosis.
    • Recently approved for unresectable giant cell tumor of bone.
  • Drugs effects:
    • Decreases serum calcium – Avoided in hypocalcemic patients.


  • Cinacalcet – Calcium-sensing receptors present on parathyroid gland.
  • Acts as “calcimimetic drug”.
  • MOA: 
    • By directly Ca2+ activates cinacalcet (calcium-sensing) receptors on parathyroid gland.
  • Uses:
    • Approved for secondary hyperparathyroidism treatment (due to chronic renal disease).
    • Hypercalcemic patients, associated with parathyroid carcinoma.
  • Drug effects:
    • Decreases PTH secretion.
    • Hypocalcemia will have opposite effect, i.e. increases PTH secretion.


  • Novel drug.
  • Strontium is incorporated into hydroxyapatite, replacing calcium.
  • MOA: Inhibits bone resorption, also stimulates bone formation.



  • Calcium – 
    • Life-saving in extreme hyperkalemia (> 7 mEg/L).
    • Used in prophylaxis & treatment of osteoporosis.
    • Calcium approved for i.v.treatment of black widow spider envenomation & magnesium toxicity.
    • Reverses some cardiotoxic effects of K+.


  • MOA: 
    • Inhibits bone resorption.
  • Uses:
    • Useful in Paget’s disease management.
    • Hypercalcemia of malignancy.
  • Adverse effect:
    • Nephrotoxicity


  • MOA: Inhibits renal Ca2+ excretion
  • Uses: Osteoporosis treatment
  • Adverse effect: Recurrent calcium stones due to hypercalciuria.


  • MOA: Inhibits bone resorption.
  • Used for osteoporosis treatment.
  • Administered by nasal route (for this indication).
  • Possess analgesic effects on bone pain from fractures.

Exam Important


  • Drugs used for treating osteoporosis are bisphosphonates, selective estrogen receptor modulators (SERM), Teriparatide, Denosumab, Osteoprotegerin, Cinacalcet, Strontium ranelate, Calcium, Gallium nitrate & Calcitonin.
  • Bisphosphonates exhibit inhibitory effect on osteoclast-mediated bone resorption.
  • Bisphosphonates cause osteoclast-mediated bone resorption, by accelerating osteoclastic apoptosis & by suppressing differentiation of osteoclast precursors to mature osteoclasts.
  • Least potent bisphosphonates are 1st generation drugs like medronate, clodronate & etidronate.
  • Longest half-life of bisphosphonate in bone is with alendronate for almost 10 years.
  • 3rd generation bisphosphonate drugs like risedronate & zoledronate are the most potent agents.
  • Bisphosphonates are used in treatment of post-menopausal & steroid-induced osteoporosis.
  • Pamidronate & zoledronate, by i.v route is preferred for treating hypercalcemia of malignancy.
  • Distinctive toxicity of bisphosphonates is esophageal irritation & ulceration.
  • Bisphosphonates are not taken by mouth & advised not to lie down, for at least half an hour.
  • 1st generation bisphosphonate results in osteomalacia.
  • On long-term bisphosphonate use, there is increased risk of atypical ‘chalkstick’ fracture of femur (subtrochanteric or shaft).
  • Estrogens inhibit bone resorptiondirectly by inhibiting osteoclast & indirectly by modulating paracrine factors.
  • Selective estrogen receptor modulators (SERM) increases anti-resorptive, suppresses pro-resorptive factor synthesis by osteoblasts & increase bone formation.
  • SERM is useful for treating postmenopausal osteoporosis.
  • Estrogen deficiency in old age results in postmenopausal osteoporosis.
  • Raloxifene, a SERM exhibits estrogen agonistic action on bone & antagonistic action on breast & endometrium.
  • Raloxifene, a SERM is a preferred drug for treatment & prevention of post-menopausal osteoporosis.
  • Bazedoxifene is a recently approved SERM for prevention of postmenopausal osteoporosis.
  • Bazedoxifene also treats vasomotor symptoms of menopause.
  • Teriparatide is a recombinant PTH1-34.
  • Teriparatide & strontium ranelate stimulates osteoblast.
  • Most osteoporotic drugs act by inhibiting osteoclast.
  • PTH in low & pulsatile dose stimulates bone formation.
  • PTH in excess causes bone resorption.
  • Teriparatide stimulates new collagenous bone.
  • Sufficient vitamin D intake & calcium is advised concurrently during teriparatide therapy.
  • On administering Teriparatide 20 mcg/d subcutaneously for 2 years, dramatically improves bone density in most bones, except distal radius.
  • Teriparatide course is followed by bisphosphonates course mainly considered for retaining & improving bone density.
  • Teriparatide is used for healing of chalk stick fractures associated with bisphosphonate therapy.
  • Denosumab is a monoclonal antibody against RANK ligand, useful for osteoporosis treatment.
  • Osteoclasts have a surface receptor named ‘receptor for activated nuclear factor κ B (RANK), which on stimulation by RANK ligand causes bone resorption.
  • Osteoprotegerin acts as a decoy receptor for RANK ligand.
  • Osteoprotegerin binds RANK receptors, preventing RANK-L binding to osteoclasts.
  • Cinacalcet is a calcium-sensing receptor present on parathyroid gland.
  • Cinacalcet acts as “calcimimetic drug”.
  • Cinacalcet is approved for secondary hyperparathyroidism treatment.
  • PTH secretion is decreased by Cinacalcet.
  • Strontium ranelate inhibits bone resorption as well as stimulates bone formation.
  • Calcium is a life-saving in extreme hyperkalemia (> 7 mEg/L).
  • Calcium is approved for i.v.treatment of black widow spider envenomation & magnesium toxicity.
  • Calcitonin inhibits bone resorption.
Don’t Forget to Solve all the previous Year Question asked on TREATMENT OF OSTEOPOROSIS

Module Below Start Quiz

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this:
Malcare WordPress Security