Denosumab After Teriparatide in Premenopausal Women with Idiopathic Osteoporosis

Context We have previously reported that teriparatide is associated with substantial increases in bone mineral density (BMD) at the lumbar spine (LS), total hip (TH) and femoral neck (FN) and small declines at the distal radius (DR) in 41 premenopausal women with idiopathic osteoporosis (IOP), all severely affected with low trauma fractures and/or very low BMD. Effects of teriparatide dissipate if not followed by antiresorptives. Objectives To assess the effects of 12 and 24 months (M) of denosumab in premenopausal women with IOP completing 24M of teriparatide. Design Preplanned phase 2B extension study Setting Tertiary referral centers Patients Premenopausal women with IOP Interventions Denosumab 60mg every 6 months for 12 and 24M Main Outcome Measures Within-group change in BMD at the LS at 12M. Secondary outcomes include change in 12M BMD at other sites, 24M BMD at all sites, trabecular bone score (TBS) and bone turnover markers (BTM). Findings After completing teriparatide, 32 participants took denosumab for 12M and 29 for 24M, with statistically significant increases in BMD at the LS (5.2±2.6% and 6.9±2.6%), TH (2.9±2.4% and 4.6±2.8%) and FN (3.0±3.8% and 4.7±4.9%). Over the entire 24M teriparatide and 24M denosumab treatment period, BMD increased by 21.9±7.8% at the LS, 9.8±4.6% at the TH and 9.5±4.7% at the FN (all p<0.0001). TBS increased by 5.8±5.6% (p<0.001). Serum BTM decreased by 75%-85% by 3M and remained suppressed through 12M of denosumab. Denosumab was generally well-tolerated. Conclusions These data support the use of sequential teriparatide and denosumab to increase BMD in premenopausal women with severe osteoporosis.

Idiopathic Osteoporosis and Nephrolithiasis: Two Sides of the Same Coin?

Idiopathic osteoporosis and nephrolithiasis are formidable health problems showing a progressive increase in their incidence and prevalence in the last decades. These temporal trends were observed in both pediatric and adult populations worldwide. Epidemiological and experimental studies indicate that both disorders show several common pathogenic environmental and genetic factors. In this review, we analyzed the clinical characteristics common to the two disorders and the state-of-the-art knowledge regarding the genetic predisposition and the environmental factors recognized as triggers in adult and pediatric ages. As a result of this work, we propose to consider idiopathic nephrolithiasis and osteoporosis as two possible expressions of a unique clinical syndrome. Accordingly, the clinical approach to both disorders should be modified in order to program an efficient primary and secondary prevention strategy.

Effect of Teriparatide on Bone Remodeling and Density in Premenopausal Idiopathic Osteoporosis: A Phase II Trial

Context Premenopausal women with idiopathic osteoporosis (IOP) have abnormal skeletal microarchitecture and variable tissue-level bone formation rate (BFR). Objectives Compare 6 months (M) of teriparatide versus placebo on areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA), bone turnover markers (BTMs) and BFR at 3M by quadruple-labeled transiliac biopsy. Characterize 12M and 24M effects of teriparatide on aBMD and whether BTMs and BFR predict response. Design 6M phase 2 randomized controlled trial (RCT) followed by open extension. Setting Tertiary referral centers. Patients Premenopausal women with IOP. Interventions A total of 41 women were randomized to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6M, those on placebo switched to teriparatide for 24M; those on teriparatide continued for 18M. Main Outcome Measures 6M RCT: Between-group differences in lumbar spine (LS) aBMD (percent change from baseline), 3M BFR, and hypercalcemia. Open-label extension: Within-group change in LS aBMD over 12M and 24M. Secondary outcomes included aBMD change at other sites and relationship between BTMs, BFR, and changes in aBMD. Findings Over 6M, LS aBMD increased by 5.5% (95% CI: 3.83, 7.19) in teriparatide and 1.5% (95% CI: −0.73, 3.83) in placebo (P = 0.007). There were increases in 3M BTMs, and BFR (cancellous and endocortical BFR: between-groups P = 0.004). Over 24M, teriparatide increased LS aBMD by 13.2% (95% CI: 10.3, 16.2), total hip by 5.2% (95% CI: 3.7, 6.7) and femoral neck by 5.0% (95% CI: 3.2, 6.7; all P ≤ 0.001). Serum N-terminal propeptides of procollagen type 1 (P1NP) and 3M endocortical BFR were moderately associated with LS aBMD response. Teriparatide was well-tolerated. Conclusions Teriparatide increased BFR and formation markers and was associated with marked aBMD improvements in most premenopausal women (82%) with IOP.