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Bisphosphonate holiday increases bone resorption rates in osteoporosis
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In postmenopausal women with osteoporosis, prolonged oral bisphosphonate use can maintain bone resorption rates within the normal reference range for premenopausal women, but a drug holiday may result in an increase in bone resorption, according to recent research.
Yair Liel, MD, of Soroka University Medical Center in Israel, and colleagues evaluated 211 women (mean age, 67.8 years) with osteoporosis prescribed oral bisphosphonates for more than 2 years to determine bone resorption rates in response to a drug holiday, to switching to IV bisphosphonate therapy or to continuing oral bisphosphonates. Urinary deoxypyridinoline cross-links were assessed in all participants.
Most participants were assigned to alendronate (86.3%), and 13.7% were assigned to risedronate; mean treatment length on oral bisphosphonates was 7.2 years at the initial urinary deoxypyridinoline cross-links assessment.
Among the cohort, 61% had urinary deoxypyridinoline cross-links level within the reference range for premenopausal women; this level was below the reference range in 7.6% and exceeded the upper limit of the reference range in 30.8% or participants. More participants assigned risedronate than alendronate had a urinary deoxypyridinoline cross-links level above the premenopausal upper reference range (43% vs. 30%), 20% above the reference range (26% vs. 16%) and 30% above the reference range (26% vs. 12%).
Data were available for 21 participants who switched from oral bisphosphonates to IV zoledronic acid; switching caused a significant decrease in mean urinary deoxypyridinoline cross-links level from 11.3 nmol/nmol creatinine to 7.95 nmol/nmol after a median follow-up of 1 year. Data were available on 22 participants who switched to a drug holiday; mean urinary deoxypyridinoline cross-links level increased from 2.9 nmol/nmol to 6.6 nmol/nmol (P < .001) after a median follow-up of 1.25 years. Mean urinary deoxypyridinoline cross-links level decreased from 6.2 nmol/nmol to 5.1 nmol/nmol after a median follow-up of 2.25 years in 25 participants who continued on oral bisphosphonate.
“The majority of the patients on long-term bisphosphonates treatment maintain normal bone turnover rates,” the researchers wrote. “‘Subclinical treatment failure’ is much more prevalent than over-suppression in patients on long-term oral bisphosphonates in a ‘real-world’ setting and may be more prevalent among risedronate-treated patients. Clinical fracture risk assessment tools and [bone mineral density] may not be timely and sensitive enough to recognize ‘subclinical treatment failure’ in patients on prolonged oral bisphosphonate treatment, which may be revealed by using bone turnover markers. Patients with ‘subclinical treatment failure’ may not be suitable for ‘drug holiday’ and could benefit from switching to parenteral treatment.” – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.
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