Optimizing Outcomes for Patients With Metabolic Bone Disease

• Introduction
  
  
• The Evolving Management of Osteoporosis: Shortcomings and Solutions
  Author: Steven T. Harris, MD, FACP
  
  
• Optimizing Therapeutic Outcomes for Patients With Paget’s Disease of Bone
  Author: Frederick R. Singer, MD
  
  
• Modifying Treatment Paradigms: Differentiating Attributes of a Novel Bisphosphonate
  Author: Graham Russell, MD, PhD
  
  
• Figures
  
  
• References
  
  

Optimizing Therapeutic Outcomes for Patients With Paget’s Disease of Bone

• Figure 1. Clinical Implications of Paget’s Disease of Bone²⁵
• Figure 2. Radiological Evidence That Bisphosphonates Restore Bone Structurally
• Figure 3. Resistance With Current Bisphosphonates³⁰
• Figure 4. Therapeutic Response of ZA and Risedronate at 2 and 6 Months³⁴
• Figure 5. Time to Loss of Therapeutic Response
  
  

Figure 1. Clinical Implications of Paget’s Disease of Bone²⁵

Photo courtesy of Pierre Delmas.

Figure 2. Radiological Evidence That Bisphosphonates Restore Bone Structurally

Photos courtesy of S.E. Papapoulos, MD.

Figure 3. Resistance With Current Bisphosphonates³⁰

ETID = etidronate; RIS = risedronate.
Adapted with permission from Miller PD et al. Am J Med. 1999;106:513-520.

Figure 4. Therapeutic Response of ZA and Risedronate at 2 and 6 Months³⁴

RIS = risedronate; SAP = serum alkaline phosphatase; ZA = zoledronic acid.
*Responder: ≥75% reduction from baseline in SAP excess.
†P = .001 vs risedronate.
Dosage: RIS: 30 mg once daily for 60 days; ZA: single IV infusion of 5 mg

Figure 5. Time to Loss of Therapeutic Response

RIS = risedronate; ZA = zoledronic acid.
Data on file, Novartis Pharmaceuticals Corporation.

Modifying Treatment Paradigms: Differentiating Attributes of a Novel Bisphosphonate

Author: Graham Russell, MD, PhD

• Figure 1. Chemical Relationships of Nitrogen-Containing Bisphosphonates
• Figure 2. Bisphosphonates Inhibit Bone Resorption In Vitro and In Vivo³⁷
• Figure 3. Distribution of 14C-Labelled ZA in the Rat Skeleton After IV Injection
• Figure 4.  Effect of ZA on Cancellous Bone of OVX Rats³⁸
• Figure 5.  Multiple Potential Binding Sites of ZA to Hydroxyapatite Mineral Surfaces
  
  

Figure 1. Chemical Relationships of Nitrogen-Containing Bisphosphonates

BPs = bisphosphonates.

Figure 2. Bisphosphonates Inhibit Bone Resorption In Vitro and In Vivo³⁷

TPTX = thyroparathyroidectomized.

Figure 3. Distribution of 14C-Labelled ZA in the Rat Skeleton After IV Injection

IV = intravenous; ZA = zoledronic acid.
From Jonathan Green 2002. Data on File. Novartis Pharmaceuticals Corporation.

Figure 4. Effect of ZA on Cancellous Bone of OVX Rats³⁸

CT = computed tomography; IV = intravenous; OVX = ovariectomized; ZA = zoledronic acid.

Figure 5. Multiple Potential Binding Sites of ZA to Hydroxyapatite Mineral Surfaces

ZA = zoledronic acid.