67. Parathyroid hormone, calcitonin and vitamin D, drugs used to treat osteoporosis

Page created on November 13, 2019. Last updated on April 25, 2022 at 10:33


See here for general info on osteoporosis.

Preventative measures:

  • Elimination of risk factors
    • Smoking
    • Alcohol
  • Physical activity
  • Calcium supplementation
    • 1 – 1,5g daily
  • Vitamin D supplementation
    • 800 international units (IU) daily


The first-line treatment of osteoporosis are bisphosphonates like alendronate. Other potential treatments include:

  • Teriparatide (parathyroid hormone analogue)
  • Oestrogens
  • Tibolone
  • Raloxifene
  • Denosumab

Strontium ranelate was pulled from the market due to increased risk for cardiovascular disease.

  • Aminobisphosphonates
    • Alendronate
    • Risedronate
    • Zoledronate
  • Simple bisphosphonates
    • Etidronate


  • Osteoporosis
  • Hypercalcaemia due to increased bone resorption
    • Tumor-induced osteolysis
    • Multiple myeloma
  • Inherited bone diseases

Zoledronate is used in hypercalcaemia, the others in osteoporosis.

Mechanism of action:

Bisphosphonates are analogues of pyrophosphate, which normally inhibits bone resorption. Unlike pyrophosphate bisphosphonates are resistant to enzymatic breakdown, so their inhibitory effect lasts longer. They form complexes with calcium in the bone matrix and are released slowly as bone is resorbed by osteoclast. When released the osteoclasts are exposed to the bisphosphonate, which inhibits further resorption.

The exact mechanism of how bisphosphonates inhibit osteoclasts differs on the exact type of bisphosphonate. Simple bisphosphonates are incorporated into ATP analogues, which accumulate and cause apoptosis of osteoclasts. Aminobisphosphonates interfere with the attachment of osteoclasts to bone.


When used to treat osteoporosis they are given orally. When used to treat hypercalcaemia of malignancy they’re given IV. Zoledronate is only given IV.

When taken orally they should be taken on an empty stomach with plenty of water while sitting or standing at least 30 minutes before breakfast. This is to prevent the tablet from getting stuck in the oesophagus, where they can cause severe problems, and to increase oral absorption, which decreases with food intake.


They have very poor absorption; <1% is absorbed orally. Around 50% of the absorbed bisphosphonate accumulates in the bone, where it can remain for years until the bone is resorbed. The rest is excreted unchanged by the kidneys.

Adverse effects:

  • Bone pain
  • GI disorders
    • Oesophagitis
  • Aseptic osteonecrosis of the jaw

Aseptic osteonecrosis is most common in high dose IV administration. The special oral dosing procedure decreases the risk for oesophagitis.


  • Renal failure
  • Hypocalcaemia


  • Osteoporosis

For severe osteoporosis or for those who don’t tolerate or have contraindications against bisphosphonates.

Mechanism of action:

Teriparatide is a fragment of parathyroid hormone, containing the first 34 amino acids of it. Parathyroid hormone generally stimulates osteoclasts, but low doses of exogenous PTH or PTH analogues paradoxically stimulates osteoblast activity. This stimulates new bone formation.


Teriparatide is given subcutaneously. Therapy should last for a maximum of 24 months, and only one 24 month-period of treatment is allowed during the life. This is because of concerns regarding long-term safety.

Vitamin D


  • Ergocalciferol
  • Alphacalciferol
  • Cholecalciferol

Ergocalciferol is the most important. It is the form of vitamin D which is found in plants. Cholecalciferol is the form of vitamin D which is synthesized in our skin.


  • Hypocalcaemia due to hypoparathyroidism
  • Osteodystrophy due to renal failure
  • Vitamin D deficiency

Mechanism of action:

Cholecalciferol is converted to calcifediol in the liver, which is further converted into calcitriol in the kidney. The main actions of calcitriol are

  • Stimulating intestinal absorption of Ca2+ and phosphate
  • Stimulating bone mineralization (at low vitamin D levels)
  • Stimulating bone resorption (at high vitamin D levels)
  • Stimulating Ca2+ reabsorption in the kidneys


Vitamin D preparations are absorbed orally as long as there is no obstructive biliary disease, as bile salts are necessary for absorption. They accumulate in fat and are eliminated by faeces.

Adverse effects:

  • Hypercalcaemia
    • GI symptoms
    • Abdominal pain
    • Kidney stones


  • Osteoporosis
    • Especially if there is especially high risk for fracture
  • Prevention of fractures in patients with bone metastases from solid tumours

Mechanism of action:

Denosumab is a monoclonal antibody which binds to RANK ligand (RANKL). RANKL is the primary signal for bone resorption. It is found on osteoblasts, where it stimulates osteoclasts.


Subcutaneous injection every 6 months. Sufficient intake of calcium and vitamin D must be ensured.

Oestrogens and raloxifene

Oestrogens inhibits osteoclasts and stimulates osteoblasts. Withdrawal of oestrogen during menopause frequently leads to osteoporosis.

Oestrogen replacement therapy is not a first-line treatment for osteoporosis for reasons described in topic 63, most importantly due to the increased risk of cancer and cardiovascular disease.

Raloxifene has the same beneficial effects as oestrogens on bone but it doesn’t increase risk of cancer and cardiovascular disease. The exception is the increased risk of thromboembolism, which also occurs with raloxifene. It is often used in patients who also require breast cancer prophylaxis.

6 thoughts on “67. Parathyroid hormone, calcitonin and vitamin D, drugs used to treat osteoporosis”

  1. Hi Nikolas,

    I this this sentence is phrased a bit inaccurate.
    “Around 50% of the administered bisphosphonate accumulates in the bone”

    Maybe better: (?)

    “Around 50% of the ABSORBED bisphosphonate accumulates in the bone”

  2. In the section of vitamin D mechanism of action you wrote: Stimulating bone resorption. I know this is true for supraphysiologically levels of Vitamin D, but did you mean to write stimulating bone mineralization in this context?

  3. hey,
    ”RANKL is the primary signal for bone resorption. It is found on osteoblasts, where it stimulates osteoclasts”

    do you mean osteoclast instead of osteoblast ?

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