Phase II Study of Alendronate Sodium in Children With High-Turnover Idiopathic Juvenile Osteoporosis

A Non-Randomized, Open-Label, Prospective, Non-Controlled, 12-Month Clinical Trial to Determine the Effects of Alendronate 35 or 70 mg/Week Depending Upon Body Weight, in Children and Adolescent With IJO

OBJECTIVES:

I. Determine the effects of alendronate sodium on skeletal remodeling and bone mineral density of the hip and spine in children with high-turnover idiopathic juvenile osteoporosis.

PROTOCOL OUTLINE:

Patients receive oral alendronate sodium weekly for 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.

Eligibility Criteria:

• 5-14 years of age
• Weight 20 kg or greater
• History of one or more atraumatic fracture
• Sexual development no greater than Tanner II
• Osteoporosis by DXA (Diagnosis of high-turnover osteoporosis with no underlying cause (e.g., malignancy, hyperthyroidism, hyperparathyroidism, or vitamin D intoxication)

Inclusion Criteria:

• Male and female children with a history of one or more atraumatic fractures, or evidence of one or more compression fractures on radiographs of the spine (reduction of >20%).
• Bone mineral density by DXA at 2 standard deviations (SD) below normal mean for age (Z-score at least 2 SD below normal mean at the lumbar spine or hip)
• Parental consent (and patient assent after age 12 years) to participate in the study.
• Sexual development at Tanner stage II or less (Prepubertal stage)
• Weight 20kg and more

Exclusion Criteria:

• History of severe gastritis or reflux

• Marked kyphoscoliosis or inability to sit or stand for at least 30 minutes.

• Abnormalities of the esophagus that delay emptying (e.g., strictures or achalasia)

• Hypersensitivity to bisphosphonates

• Uncorrected hypocalcemia

• History of gastric or duodenal ulcers

• Renal dysfunction as indicated by serum Creatinine greater than 1.5 mg/dL

• Liver dysfunction as indicated by serum SGPT greater than 2 times upper limit of normal for age or serum total bilirubin greater than 2.0 mg/dL

• Diagnosis of osteogenesis imperfecta (including family history) or blue sclerae or deafness

• Diagnosis of active rickets, osteomalacia, or bone alkaline phosphatase > 2 times normal for age

• Severe gastritis or reflux

• Pregnancy

• Anorexia Nervosa

  • Prior/Concurrent Therapy-

• Prior course of prednisone allowed

• No concurrent prednisone except inhaled steroids

• No concurrent high-dose glucocorticoids

• No concurrent salmon calcitonin

• No other concurrent bisphosphonates

• No concurrent long-term anti-seizure medication