Bone Metabolism and Osteoporosis

Question 1

The two main disorders of bone metabolism that occur in children are what?

Answer 1

Rickets and osteoporosis.

Question 2

What are the two most common forms of rickets?

Answer 2

Vitamin D deficiency rickets and hypophosphataemic rickets.

Question 3

To reduce the risk of osteoporosis, the doses of what should be as low as possible?

Answer 3

Corticosteroids.

Question 4

What is used by specialists to lower the plasma-calcium concentration in children with hypercalcaemia associated with malignancy?

Answer 4

Calcitonin either synthetic or recombinant as it is involved with parathyroid hormone in the regulation of bone turnover and hence maintenance of calcium balance and homoestasis.

Question 5

Osteoporosis occurs most commonly in what patient groups? (3)

Answer 5

1. Postmenopausal women
2. Men over 50 years
3. Patients taking long-term oral corticosteroids (glucocorticoids).

Question 6

Risk factors for osteoporosis include what? (10)

Answer 6

1. low BMI
2. Smoker
3. Excess alcohol
4. Lack of physical activity
5. Vit D deficiency
6. Low calcium intake
7. Family history
8. Previous facture at site.
9. Diabetes
10. RA

Question 7

What is first-line in postmenopausal women for prevention and treatment of osteoporosis?

Answer 7

Oral bisphosphonates, alendronic acid and risedronate sodium are considered as first-line choices for most patients with postmenopausal osteoporosis due to their broad spectrum of anti-fracture efficacy.

Question 8

What is an additional option for postmenopausal osteoporosis other than oral or IV bisphosponates?

Answer 8

Hormone replacement therapy (HRT) is an additional option. The use of HRT for osteoporosis is generally restricted to younger postmenopausal women with menopausal symptoms who are at high risk of fractures. This is due to the risk of adverse effects such as cardiovascular disease and cancer in older postmenopausal women and women on long-term HRT therapy.

Or Denosumab or Raloxifene hydrochloride.

Question 9

What is the mechanism of action of bisphosphonates?

Answer 9

They are ingested by osteoclasts, the cells that break down bone tissue and inihibit their function.

Question 10

What are the side effects of bisphosphonates?

Answer 10

Orally they can cause upset stomach, inflammation and erosions of the esophagus. Remain standing or seated upright for 30 - 60 minutes after taking the medication.

When given IV for treatment of cancer can cause osteonecrosis of the jaw.

(Recent studies suggest potential for AF in women specifically with zoledronate and alendronate).

Question 11

How does teriparatide work?

Answer 11

Terparatide is a biologic medicine.

It is a portion of human parathyroid (PTH) that stimulated new bone formation.

Question 12

How does teriparatide work?

Answer 12

Terparatide is a biologic medicine.

It is a portion of human parathyroid (PTH) that stimulated new bone formation.

Question 13

Glucocorticoid therapy is associated with bone loss and increased risk of fractures. The greatest rate of bone loss occurs when?

Answer 13

Glucocorticoid therapy is associated with bone loss and increased risk of fractures. The greatest rate of bone loss occurs early after initiation of glucocorticoids and increases with dose and duration of therapy. Bone-protection treatment should be started at the onset of therapy in patients who are at a high risk of fracture.

Question 14

Women aged 70 years or over, or with a previous fragility fracture, or taking large doses of glucocorticoids (prednisolone ≥___mg daily or equivalent) are at high risk of fractures and should be assessed for prophylactic bone-protection .

Answer 14

Women aged 70 years or over, or with a previous fragility fracture, or taking large doses of glucocorticoids (prednisolone ≥7.5 mg daily or equivalent) are at high risk of fractures and should be assessed for prophylactic bone-protection .

Question 15

Women aged 70 years or over, or with a previous fragility fracture, or taking large doses of glucocorticoids (prednisolone ≥___mg daily or equivalent) are at high risk of fractures and should be assessed for prophylactic bone-protection .

Answer 15

Women aged 70 years or over, or with a previous fragility fracture, or taking large doses of glucocorticoids (prednisolone ≥7.5 mg daily or equivalent) are at high risk of fractures and should be assessed for prophylactic bone-protection .

Question 16

Oral bisphosphonates, alendronic acid or risedronate sodium are recommended as first-line treatments for osteoporosis in men.

Men having long-term androgen deprivation therapy for what have an increased fracture risk?

Answer 16

Prostate cancer.

Question 17

How does denosumab work?

Answer 17

It is a human monoclonal antibody that inihibits osteoclast formation, function, and survival, thereby decreasing hone resorption.

Alternative for patients who cannot tolerate bisphophonates etc.

Given every 6 months, supplement with calcium and vitamin D.

Question 18

There is some evidence to suggest that patients can benefit from a bisphosphonate-free period as their therapeutic effects last for some time after cessation of treatment. How often should treatment be reviewed?

Answer 18

after 5 years with alendronic, risedronate or ibandronic and after 3 years with zoledronic.

Question 19

What preparations used for heartburn can cause bone loss?

Answer 19

Anatacids that contain aluminum:

“In addition, the small doses of aluminum-containing antacids also affected the metabolism of calcium and phosphorus, the primary effect being complexation of phosphorus in the intestine leading to phosphorus depletion. This change in phosphorus metabolism was associated with an increase of the urinary and fecal calcium excretion resulting in a negative calcium balance.”

https://www.ncbi.nlm.nih.gov/pubmed/3886758

Also some evidence so can PPIs!

Question 20

Which drugs used for the prevention of rejection in organ transplantation can cause bone loss?

Answer 20

Cyclosporine and tacrolimus.

(Ciclosporin does not cause bone marrow suppression, unlike other immunosuppresants).

Question 21

What anticoagulant can cause bone loss?

Answer 21

Heparin:
Heparin causes increased bone resorption by stimulating osteoclasts and suppressing osteoblast function, leading to decreased bone mass. Other proposed mechanisms include depletion of mast cells in bone marrow and enhancement of parathyroid hormone (PTH) function, an important regulator of calcium in the body.

Question 22

What medication used in heart failure can cause bone loss?

Answer 22

Loop diuretics like furosemide: increased calcium loss.

Question 23

What diabetes drugs can cause bone loss?

Answer 23

Thiazolidinediones such as pioglitazone and rosiglitazone:

TZDs exert their antidiabetic effects by activating peroxisome proliferator-activated receptor-γ (PPAR-γ) nuclear receptor, which controls glucose and fatty acid metabolism.

In bone, PPAR-γ controls differentiation of cells of mesenchymal and hematopoietic lineages. PPAR-γ activation with TZDs leads to unbalanced bone remodeling: bone resorption increases and bone formation decreases.

Question 24

Why do thiazides slow bone loss?

Answer 24

Reduced calcium excretion.

Question 25

What is the half life of alendronic acid?

Answer 25

Unlike with most drugs, the strong negative charge on the two phosphonate moieties limits oral bioavailability, and, in turn, the exposure to tissues other than bone is very low. After absorption in the bone, alendronate has an estimated terminal elimination half-life of 10 years (126 months).

Zoledronic acid: 146 hours.
Etidronic acid: 3 hours
Risedronic acid: 1.5 hours.

Question 26

Non-nitrogen containing bisphosphonates - such as etidronic acid- work how?

Answer 26

Form a toxic version of ATP which induces osteoclast apoptosis.

Question 27

Ranitidine has what effect on the bioavailability of bisphosphonates?

Answer 27

Increased