Short summary

Osteoporosis is a chronic disease often treated with bisphosphonates. Current guidelines suggests that patients should be treated for a five year period, seeing that long term fracture prevention are obtained even after specific fracture prophylactic treatment have been stopped. During drug holidays, patients are followed closely with DXA scans to evaluate any signs of significant bone loss or changes in the fracture risk profile. A significant fall in bone mineral density (BMD) results in the patients resuming treatment. Currently we have no or very little knowledge on which risk factors predispose to a fall in BMD after treatment with bisphosphonates is paused.

Via various administrative databases and patient medical chart reviews we identify the women that are on or have been on a treatment pause from Zoledronic acid. Their risk factors (smoking, family disposition, alcohol intake etc.) at baseline and at the start of the treatment pause is recorded from the patients charts. Comparing the BMD of the identified women before and during treatment pause will aid us in identifying which risk factors predispose to a significant fall in BMD. We therefor hope to be able to predict which patients will and who will not benefit from drug holiday.

Rationale

Osteoporosis is a chronic disease which is often treated with bisphosphonates administered either orally or intravenously. Unlike most other chronic diseases the effect of lifelong treatment with bisphosphonates on osteoporosis is unknown.

In Denmark men and women are DXA-scanned if they have one or more risk factors of a osteoporotic fracture. A DXA-scan measures the bone mineral density (BMD), and calculates a t-score, which compares the measured BMD to peak BMD in the same sex. A t-score below -2,5 or previous fractures in the hip or spine can be used to diagnose an individual with osteoporosis.

Few studies on long term treatment with bisphosphonates have been conducted. A large study from 2006 found no difference in amount of fractures when treated with bisphosphonates in five years compared to long term treatment. A study from 2012 found a reduced risk of compression fractures when treated with intravenous bisphosphonates over a nine year period compared to six years treatment. There was no significant difference when looking at fractures in the extremities.

In Denmark patients are currently treated three to five years with bisphosphonates. An extension of the duration will depend on the DXA-scan result and individual risk factors of the patient. Some patients will discontinue treatment after five years, and these patients will have a DXA-scan and evaluation in the department of endocrinology one year after treatment pause. A significant fall in BMD or new fractures will often result in the patient resuming treatment.

It is known that risk factors such as age, smoking,  early menopause, low BMI and treatment with prednisolone increases the risk of osteoporosis, but to our knowledge, there are no knowledge on which risk factors predispose a fall in BMD after ended treatment with bisphosphonates.

Description of the cohort

Patients with osteoporosis currently treated at the department of endocrinology are included in the study and will be identified via two different databases.

Only patients that have been treated with zoledronic acid are included. These patients are identified via "budget- og økonomiafdelingen", the economics department at the hospital.

Through the local DXA database, we can identify patients who have had a DXA-scan 12-36 months after their latest treatment with zoledronic acid.

Patients undergoing treatment with prednisolone and patients having other bone metabolic diseases will be excluded from the study since these patients are more likely to develop a low BMD. We also exclude patients who have died or moved to another region. Finally we exclude patients with another ethnicity than caucasian and all male patients as well as premenopausal women, so that out study population will be uniform.

Data and biological material

The extraction from "økonomi- og budgetafdelingen" will provide dates of the each administration of zoledronic acid. These data are available from 1/1-2007 and are continuously updated. Patients where zoledronic acid was administered more than 12 months prior to data collection is presumed to be undergoing treatment pause, or have changed to other treatment options.

Data regarding BMD, weigh, height and etnicity is obtained via our local DXA-database, where the patients will be identified via CPR-number.

Information regarding risk factors for osteoporosis, duration of treatment and other information that can lead to exclusion from the study is obtained via the patient's electronic hospital records.

Data with personal details (e.g. CPR-number) will be handled by one person only and the other collaborating researchers will first be given access to data when these have been pseudo-anonymised. Data will be stored via OPEN using REDCap, ensuring that all data containing personal data, are stored in a secure manner.

Collaborating researchers and departments

Department of Endocrinology, Odense University Hospital

• Consultant Pernille Hermann, PhD
• PhD-student Lars Folkestad