• 1
    Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab. 2010; 95:155565.
  • 2
    Boonen S, Laan RF, Barton IP, Watts NB. Effect of osteoporosis treatments on risk of non-vertebral fractures: review and meta-analysis of intention-to-treat studies. Osteoporos Int. 2005; 16:12918.
  • 3
    Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of post-menopausal osteoporosis. N Engl J Med. 2007; 356:180922.
  • 4
    Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361:75665.
  • 5
    Deal C. Potential new drug targets for osteoporosis. Nat Clin Pract Rheumatol. 2009; 5:207.
  • 6
    Yasuda Y, Kaleta J, Brömme D. The role of cathepsins in osteoporosis and arthritis: rationale for the design of new therapeutics. Adv Drug Deliv Rev. 2005; 57:97393.
  • 7
    Drake FH, Dodds RA, James IE, et al. Cathepsin K, but not cathepsins B, L, or S, is abundantly expressed in human osteoclasts. J Biol Chem. 1996; 271:125116.
  • 8
    Gelb BD, Shi GP, Chapman HA, Desnick RJ. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Science. 1996; 273:12368.
  • 9
    Adami S, Supronik J, Hala T, et al. Effect of one year treatment with the cathepsin-K inhibitor, balicatib, on bone mineral density (BMD) in postmenopausal women with osteopenia/osteoporosis. Paper presented at: American Society for Bone and Mineral Research 28th Annual Meeting; September 2006; Philadelphia, PA. Abstract 1085.
  • 10
    Bone HG, McClung MR, Roux C, et al. Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res. 2010; 25:93747.
  • 11
    Papanastasioiu P, Ortmann CE, Olson M, Vigneron A, Trechsel U. Effect of three month treatment with the cathepsin-K, balicatib, on biochemical markers of bone turnover in postmenopausal women: evidence of uncoupling of bone resorption and bone formation. J Bone Miner Res. 2006; 21:S59.
  • 12
    Peroni A, Zini A, Braga V, Colato C, Adami S, Girolomoni G. Drug-induced morphea: report of a case induced by balicatib and review of the literature. J Am Acad Dermatol. 2008; 59:1259.
  • 13
    Kumar S, Dare L, Vasko-Moser JA, et al. A highly potent inhibitor of cathepsin K (relacatib) reduces biomarkers of bone resorption both in vitro and in acute model of elevated bone turnover in vivo in monkeys. Bone. 2007; 40:12231.
  • 14
    Yamada H, Mori H, Nakanishi Y, et al. Orally active cathepsin K inhibitor, ONO-5334, potently improved bone mineral density not only in trabecular bone but also in cortical bone in ovariectomized cynomolgus monkeys. Paper presented at: The American Society for Bone and Mineral Research 2009 Annual Meeting. September 2009; Denver, CO. Abstract A09002146.
  • 15
    Nagase S, Ohyama M, Hashimoto Y, Small M, Kuwayama T, Deacon S. Pharmacodynamic effects on biochemical markers of bone turnover and pharmacokinetics of the cathepsin K inhibitor, ONO-5334, in an ascending multiple-dose. Phase 1 study. J Clin Endocrinol Metab. 2012; 97:31125.
  • 16
    Eastell R, Nagase S, Ohyama M, Small M, Sawyer J, Boonen S, Spector T, Kuwayama T, Deacon S. Safety and efficacy of the cathepsin K inhibitor ONO-5334 in postmenopausal osteoporosis: the OCEAN study. J Bone Miner Res. 2011; 26:130312.
  • 17
    Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with post-menopausal osteoporosis: a randomized controlled trial. JAMA. 1999; 282:134452.
  • 18
    Eisman JA, Bone HG, Hosking DJ, et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res. 2011; 26:24251.
  • 19
    Rizzoli R, Greenspan SL, Bone G 3rd, et al. Two-year results of once-weekly administration of alendronate 70 mg for the treatment of postmenopausal osteoporosis. J Bone Miner Res. 2002; 17:198896.
  • 20
    Rosen CJ, Hochberg MC, Bonnick SL, et al. Fosamax Actonel Comparison Trial Investigators. Treatment with once-weekly alendronate 70 mg compared with once-weekly risedronate 35 mg in women with postmenopausal osteoporosis: a randomized double-blind study. J Bone Miner Res. 2005; 20:14151.
  • 21
    Brown JP, Prince RL, Deal C, et al. Comparison of the effect of denosumab and alendronate on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded. Phase 3 trial. J Bone Miner Res. 2009; 14:134.
  • 22
    Nagase S, Hashimoto Y, Small M, et al. Effect of a new sustained-release formulation of the novel cathepsin K inhibitor, ONO-5334, on serum and urine biochemical markers of bone turnover in healthy post-menopausal women. Paper presented at: American Society of Bone and Mineral Research 2011 Annual Meeting; September 2011; San Diego, CA.
  • 23
    Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005; 90:1294301.
  • 24
    Ninomiya JT, Tracy RP, Calore JD, Gendreau MA, Kelm RJ, Mann KG. Heterogeneity of human bone. J Bone Miner Res. 1990; 5:9338.
  • 25
    Stoch SA, Zajic S, Stone J, et al. Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies. Clin Pharmacol Ther. 2009; 86:17582.
  • 26
    Cusick T, Chen CM, Pennypacker BL, et al. Odanacatib treatment increases hip bone mass and cortical thickness by preserving endocortical bone formation and stimulating periosteal bone formation in the ovariectomized adult rhesus monkey. J Bone Miner Res. 2012; 27:52437.
  • 27
    Jerome C, Missbach M, Gamse R. Balicatib, a cathepsin K inhibitor, stimulates periosteal bone formation in monkeys. Osteoporos Int. 2012; 23:33949.
  • 28
    Goh SK, Yang KY, Koh JS, et al. Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br. 2007; 89:34953.
  • 29
    Papapetrou PD. Bisphosphonate-associated adverse events. Hormones (Athens). 2009; 8:96110.
  • 30
    Rünger TM, Adami S, Benhamou CL, et al. Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatib. J Am Acad Dermatol. 2012; 66:e8996.