Trial of Lithium Carbonate for Treatment of Osteoporosis-pseudoglioma Syndrome
Condition: Osteoporosis Pseudoglioma
MeSH terms: Osteoporosis; Osteogenesis Imperfecta; Blindness; Spasms, Infantile; Genetic Diseases, X-Linked
Study type: Interventional

Summary: 
      This was a pilot study of 10 patients with Osteoporosis-pseudoglioma syndrome (OPPG) from the
      Old Order Mennonite community and 16 controls, who did not have OPPG. Five of the 10 OPPG
      patient elected to participate in the Lithium trial and 5 participated only in baseline data
      (labs, pQCT). The 5 with OPPG who were given lithium for 6 months had both dual energy xray
      absorptiometry (DXA), peripheral quantitative computerized tomography (pQCT) and lab
      assessment at baseline and 6 months. Studies in the mouse model of OPPG showed that lithium
      normalized their bone strength. Controls (n=16) were recruited from the Old Order Mennonite
      community, to minimize the effects of environmental and lifestyle factors. The controls were
      not be given lithium. The age range of participants was 4-64 years.
    

Detailed description: 
      Osteoporosis-pseudoglioma (OPPG) syndrome is a very rare genetic disorder (approximately 50
      cases have been reported worldwide) due to mutations in the LRP5 gene, causing blindness from
      birth and fragile bones (osteoporosis)in early childhood. The bony fragility can lead to
      recurrent fractures of major bones such as the hip (femur) and spine, leaving some children
      in wheelchairs.

      Treatment to strengthen the bones in OPPG has primarily been with osteoporosis medications
      used in other fragile bone disorders of childhood and in adults, namely the bisphosphonates
      (eg. pamidronate, alendronate). These drugs have helped the bone strength in OPPG somewhat
      but have not prevented all fractures. We have observed fractures of the hip in 3 children
      with OPPG who we have treated, in spite of their attaining normal bone density (determined by
      DXA, dual xray absorptiometry) with bisphosphonates. Therefore, new treatments for OPPG are
      greatly needed and new methods besides DXA are needed to monitor bone strength on treatment.

      A mouse model of OPPG has been created. In the mouse model of OPPG, lithium dramatically
      improved their bones, returning them to normal strength and preventing fractures. Lithium,
      which is used for people with psychiatric disease, is known to lead to higher bone strength
      and reduced fractures in people who are on it for psychiatric disease. Lithium has been used
      safely and is approved for children 12 and above. The theory is that lithium will improve
      bone strength in OPPG in humans, as it has in the mouse, by stimulating bone production
      bypassing the genetic defect in OPPG.

      In this study, we recruited 10 patients with OPPG and treated those who agreed (n=5) with
      lithium for 6 months, monitoring the response of the bones by both DXA and pQCT (peripheral
      quantitative computed tomography), the latter which gives information about bone quality. An
      IND was obtained to use lithium in this study.
    

Intervention name(s): Lithium
Intervention type(s): Drug
Intervention description(s): lithium will be given for 6 months to patients with OPPG, starting at a low dose of 2.5 mg/kg daily, gradually increasing until a lithium blood level of 0.3-0.6 ng/dl is achieved.
Other intervention name(s): lithium carbonate or lithium citrate will be used
Intervention MeSH terms: Lithium Carbonate
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Osteoporosis-pseudoglioma syndrome, OPPG, LRP5 mutation