Effects of Denosumab Drug Holiday

Presentation Number: SUN 326
Date of Presentation: April 2nd, 2017

Vishnu Priya Pulipati*1 and Pooja Luthra2
1University of Connecticut Health Center, Farmington, CT, 2UConn Health, Farmington, CT


Back ground: Osteoporosis causes low bone mass and microarchitecture deterioration leading to increased incidence of fractures. There are concerns of side effects with long term use of antiresorptives. This case highlights the effect of drug holiday from Denosumab.

Clinical case: A 54-year-old female with Multiple sclerosis and severe osteoporosis with fragility fractures was treated with Fosamax for 15 years, Teriparatide for 2 years and Denosumab from September 2012 till October 2015. She was also on adequate calcium and Vitamin D3.

In October 2015, DXA scan showed L1-L4 BMD 0.931g/cm2, T score -2.1, a 6.8% increase from previous BMD in 2014 and a 16.2% increase from baseline study in 2011. Left femur neck BMD 0.716g/cm2, no significant change from previous BMD or baseline study. Right femur neck BMD 0.721g/cm2, no significant change from previous BMD but a 11.3% increase from baseline in 2011.

She was then placed on a holiday from Denosumab for 1 year from 2015 to 2016.

Repeat DXA in 2016 was compared to the prior study from 2015, L1-L4 BMD 0.780g/cm2, T score -3.3, a decrease of 16.2%. Left femur neck BMD 0.553g/cm2, decrease of 22.8% , Right femur neck BMD 0.558g/cm2, decrease of 22.6%.

Labs in October 2016 showed normal CBC, TSH, calcium, Vitamin D, SPEP and IPEP. Serum Collagen type I C-telopeptide [CTx] was high at 774pg/ml [prior CTx on Prolia in 2015 was 209pg/ml].

Discussion: Denosumab is a human monoclonal antibody that inhibits RANK ligand. It is approved by FDA to prevent fractures in post-menopausal women and men with osteoporosis, women on aromatase inhibitor therapy for breast cancer and in men on androgen deprivation therapy for prostate cancer. In the FREEDOM trial [Fracture reduction Evaluation of Denosumab in Osteoporosis every 6 months] Denosumab compared to placebo, reduced vertebral fracture incidence by 68% [p <0.001] and hip fracture by 40% [p <0.001]. Over 3 years, it increased the lumbar spine BMD [22.4%, p <0.0001] and total hip BMD [14.3%, p <0.0001]. It improves CTX after 1 month of use and this is sustained for 6 months. Adverse effects are hypocalcemia, osteonecrosis of jaw [0 to 2%], unusual thigh bone fractures and serious skin infections. The effects are reversible as it has no affinity for bone and hence there is no residence in skeleton. It is in circulation for a total of 6 months. After 12-months of drug holiday, BMD was noted to decline by 6.6% at lumbar spine and 5.3% at total hip. BMD returned to values near baseline after 24 months of drug holiday.

Conclusion: In the Freedom Extension Study, treatment for up to 8 years with Denosumab, was associated with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile. In view of rapid reversal of effects of Denosumab, in patients at high risk of fractures, it is appropriate to continue longer duration of treatment.


Nothing to Disclose: VPP, PL