Bisphosphonate infusion guideline

Indications for IV bisphosphonates:

1. Intolerance of oral bisphosphonates
2. Falling BMD or fracture while on oral bisphosphonates with evidence of inadequate supression of urine NTX. uNTX >25 nmol/mmol creatinine (reference range is <51 nmol/mmol creatinine)
3. Hiatus hernia, gastromucosal irritation, dysphagia, oesophageal disease, gastritis, duodenitis, or gastrointestinal ulcers.[1]

Contraindications

Creatinine clearance <35ml/min
- Planned dental surgery [2]
- Poor dentition [2]
  - Check with dentist prior to commencing treatment
  - Maintain good oral hygiene, have annual dental check-ups
  - If loosening of teeth, oral pain or swelling, inform their dentist and doctor

Tests prior to infusion

- Ensure vitamin D replete (25-OH VitD above 40-50nmol/L) and not hypocalcaemic
- Urine NTX recorded at baseline. This is collected as a 2nd morning urine sample in a 10ml universal container. It can be ordered on ICE.

How to arrange admission

Referral letter to Endocrine SpR in charge of admission for infusion of 5mg Zoledronate

Administration

1. 5mg zolendronate IV over at least 15mins
2. On discharge BNF recommends 500mg elemental calcium twice daily with vitamin D for 10 days (if not hypercalcaemic). Use any calcium preparation available from Pharmacy, e.g. Calcichew

Follow-up

1. Annual followup appointment in Metabolic Bone Clinic (BOEC)
2. Prior to appointment repeat U&E, Ca2+, Pi, Mg2+,, ALP, 25OHVitD, PTH and urine NTX
3. If NTX remains in lowest quartile <12 nmol/mmol creatinine repeat uNTX in 1 year
4. If NTX greater than 12 nmol/mmol creatinine repeat zelendronate infusion.
5. Repeat DEXA BMD scan every 2 years

[1] Green et al., 2010 suggested there may be a small increase in the risk of oesophageal cancer in patients who had taken oral bisphosphonates for more than five years compared with a group who had not take oral bisphosphonates. A subsequent study of patients in the UK General Practice Research Database cohort of 40,000 patients treated with oral bisphosphonates followed over 4½ years found the use of oral bisphosphonates was not significantly associated with incident esophageal or gastric cancer, Cardwell et al., 2010.

[2] Osteonecrosis of the jaw has been reported, especially in patients also receiving steroids, radiotherapy, and chemotherapy who have had invasive dental surgery. The onset can occur from months to years after the start of bisphosphonate therapy (Khosla et al. 2007). A review of clinical trials by Grbic et al found that of 5,903 patients with osteopaenia or osteoporosis who received zolendronate in five clinical trials, ONJ incidence was less than one in 14,200 patient treatment-years.

References

Cardwell et al. JAMA. 2010 Aug 11;304(6):657-63. Exposure to oral bisphosphonates and risk of esophageal cancer.

Grbic et al., J Am Dent Assoc. 2010 Nov;141(11):1365-70. The incidence of osteonecrosis of the jaw in patients receiving 5 milligrams of zoledronic acid: data from the health outcomes and reduced incidence with zoledronic acid once yearly clinical trials program.

Green J, Czanner G, Reeves G, Watson J, Wise L, Beral V. Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort. BMJ. 2010 Sep 1;341:c4444. doi: 10.1136/bmj.c4444.

Khosla S et al 2007 Bisphosphonate-Associated Osteonecrosis of the Jaw: Report of a Task

Force of the American Society for Bone and Mineral Research J Bone Miner Res 2007;22:1479–1491

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