Calcitonin and Teriparatide

Calcitonin and parathyroid hormone are both involved in regulating turnover of bone and calcium homoeostasis.

• Calcitonin is a peptide hormone which binds to receptors on osteoclasts and inhibits bone resorption.
• Teriparatide is a recombinant fragment of human parathyroid hormone (PTH) which acts like endogenous PTH. It regulates calcium and phosphate metabolism in bone and kidney. The main effect of PTH and teriparatide is to stimulate new bone formation by increasing osteoblastic activity.

Therapeutically calcitonin has a number of suggested indications (see clinical scenarios below) backed up by limited clinical trial data. Teriparatide and calcitonin are usually initiated by specialists (see below).

Patients at high risk of osteoporosis

Calcitonin may be considered as second line treatment for those at high risk of osteoporosis - but unsuitable for biphosphonates.² However calcitonin is not considered in the NICE guidelines or forthcoming NICE appraisals.³ Calcitonin is mentioned in the Royal College of Physicians guidelines of 2001.⁴ Individuals may be at risk for a variety of reasons determined from the history:

• Female gender (postmenopausal women at high risk but consider also hypogonadism in men and women)
• Social factors (smoking, sedentary lifestyle)
• Family history of osteoporosis
• Certain medications (glucocorticoids, some anticonvulsants, methotrexate, heparin, medroxyprogesterone acetate, thyroid supplements)
• Diseases associated with excess bone loss (hyperthyroidism, inflammatory bowel disease, hyperparathyroidism, malnutrition, chronic liver disease etc)
• Cancer especially those who have had chemotherapy
• Racial factors - osteoporosis more common in Caucasian patients and those of Asian origin
• Immobility (spinal cord injuries, stroke etc)

See osteoporosis for the assessment of risk.

Postmenopausal osteoporosis

Calcitonin may be used if unsuitable for biphosphonates in postmenopausal osteoporosis to prevent vertebral fractures.
The evidence suggests that calcitonin reduces vertebral fractures when compared with placebo in postmenopausal women.^4,5 It should be given with calcium and vitamin D supplements.

Paget's disease of bone (Osteitis deformans)

Calcitonin is given subcutaneously or intramuscularly 3 times weekly according to response in adults (those aged over 18 years). Biphosphonates can again be used but calcitonin is used in mild disease to help control bone pain, reduce alkaline phosphatase levels and for hypercalcaemia.¹ It is one of a number of different drugs and measures used to treat Paget's disease of the bone.

Hypercalcaemia

This may be associated with a number of different malignancies including for example multiple myeloma. It also results from other conditions such as hyperparathyroidism. Hypercalcaemia may be associated with a variety of symptoms and complications and treatment with calcitonin may be indicated for symptoms and to prevent complications.

Prevention of bone loss through immobility

Use of calcitonin by injection daily for 2-4 weeks is used until patients are fully mobile.

Other clinical scenarios

• After hip arthroplasty: A clinical trial of calcitonin in postmenopausal women improved clinical outcome and reduced pain.⁶
• Osteoarthritis: in a randomised controlled trail calcitonin appeared to reduce cartilage degradation.⁷
• Vertebral fractures: if other analgesics are ineffective calcitonin may be used to reduce pain.²

Postmenopausal osteoporosis

Teriparatide is recommended in particular circumstances outlined in the NICE guidance of January 2005.³ It is recommended for secondary prevention (that is in those postmenopausal women who have already had a fracture) in over 65 year old women:

• When biphosphonates have not worked* or are not tolerated;
• When they have a very high risk of fracture (T score -4 SD or below) or a T score of -3 SD and below WITH 2 fractures AND at least one of the additional risk factors for biphosphonates (including BMI <19, mother with hip fracture under 75, early untreated menopause, immobility BUT excluding medical conditions putting them at risk of osteoporosis).

*Defined as 1 year of treatment with a fracture and falling bone density.

It is important to remember that patients on treatment for osteoporosis should be followed up and monitored so that failure of treatment can be identified and patients referred for consideration of second line treatments. Further guidance on primary and secondary prevention of osteoporosis is awaited which may help inform risk assessment, monitoring and identification of treatment failure.³