Effects of sequential osteoporosis treatments on trabecular bone in adult rats with low bone mass

Summary   We used an osteopenic adult ovariectomized(OVX) rat model to evaluate various sequential treatmentsfor osteoporosis, using FDA-approved agents with complementary tissue-level mechanisms of action. Sequential treatment for 3 months each with alendronate (Aln), followed byPTH, followed by resumption of Aln, created the highesttrabecular bone mass, best microarchitecture, and highestbone strength. 
Introduction  Individual agents used to treat human osteoporosis reduce fracture risk by ∼50–60 %. As agents that act withcomplementary mechanisms are available, sequential therapies that mix antiresorptive and anabolic agents could improvefracture risk reduction, when compared with monotherapies.
Methods  We evaluated bone mass, bone microarchitecture,and bone strength in adult OVX, osteopenic rats, duringdifferent sequences of vehicle (Veh), parathyroid hormone(PTH), Aln, or raloxifene (Ral) in three 90-day treatmentperiods, over 9 months. Differences among groups wereevaluated. The interrelationships of bone mass andmicroarchitecture endpoints and their relationship to bonestrength were studied. 
Results  Estrogen deficiency caused bone loss. OVX rats treated with Aln monotherapy had significantly better bone mass,microarchitecture, and bone strength than untreated OVX rats.Rats treated with an Aln drug holiday had bone mass andmicroarchitecture similar to the Aln monotherapy group butwith significantly lower bone strength. PTH-treated rats hadmarkedly higher bone endpoints, but all were lost after PTHwithdrawal without follow-up treatment. Rats treated withPTH followed by Aln had better bone endpoints than thosetreated with Aln monotherapy, PTH monotherapy, or an Alnholiday. Rats treated initially with Aln or Ral, then switched toPTH, also had better bone endpoints, than monotherapy treatment. Rats treated with Aln, then PTH, and returned to Alnhad the highest values for all endpoints. 
Conclusion   Our data indicate that antiresorptive therapy canbe coupled with an anabolic agent, to produce and maintainbetter bone mass, microarchitecture, and strength than can beachieved with any monotherapy.