Prevention of Falls and Fractures in Old People by Administration of Calcium and Vitamin D. Randomized Clinical Trial (ANVITAD)

• Incidence of spontaneous falls. [ Time Frame: 24 months. ] [ Designated as safety issue: No ]
  The primary variable will be the incidence of spontaneous falls according to the FICSIT (Frailty and Injury: Cooperative Study of Intervention Techniques) definition: "Unintentionally coming to rest on the ground, floor, or other lower level. Coming to rest against furniture or a wall was not counted as a fall".
  
  

• Consequence of falls. [ Time Frame: 24 months. ] [ Designated as safety issue: No ]
  Bone fractures at any location, need for healthcare, need for hospitalization, bed-ridden.
  
  
• Change in calcidiol [25(OH)D3] plasma levels [ Time Frame: 18 months. ] [ Designated as safety issue: No ]
  Determined by RIA (Vitamin D deficiency is defined as a calcidiol plasma level lower than 10ng/ml).
  
  
• Change in bone mass (bone density or mineral content). [ Time Frame: 24 months. ] [ Designated as safety issue: No ]
  By densitometry (risk of fracture). Osteoporosis will be diagnosed based on a densitometry T-score of less than 2.5 in the vertebral column, according to WHO criteria.
  
  
• Change in muscle strength in the dominant hand. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  Determined by dyanometry (with a mean of 3 attempts to obtain a muscle strength measurement).
  
  
• Changes in musculoskeletal function. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  By the timed up and go test (the elderly person gets up from a chair with arms, walks three meters, turns round, walks back and sits down again). Taking more than 20 seconds indicates a high risk for falls.
  
  
• Serious adverse events or any other adverse event. [ Time Frame: 24 months. ] [ Designated as safety issue: Yes ]
  An adverse event is considered as any untoward medical occurrence in any patient included in the study which does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product.
  
  

Background:

There are many studies that associate vitamin D serum levels in older persons with muscle strength, physical performance and risk of fractures and falls. However, current evidence is insufficient to make a general recommendation for administrating calcium and vitamin D to older persons. The objective of this study is to determine the effectiveness of calcium and vitamin D supplementation in improving musculoskeletal function and decreasing the number of falls in person aged over 65 years.

Design:

Phase III, randomized, double blind, placebo-controlled trial to evaluate the efficacy of already marketed drugs in a new indication. It will be performed at Primary Care doctor visits at several Healthcare Centers in different Spanish Health Areas. A total of 704 non-institutionalized subjects aged 65 years or older will be studied (sample size calculated for a statistical power of 80%, alpha error 0.05, annual incidence of falls 30% and expected reduction of 30% to 20% and expected loss to follow up of 20%). The test drug containing 800 IU of vitamin D and 1000 mg of calcium will be administered daily. The control group will receive a placebo. The subjects will be followed up over two years. The primary variable will be the incidence of spontaneous falls. The secondary variables will include: consequences of the falls (fractures, need for hospitalization), change in calcidiol plasma levels and other analytical determinations (transaminases, PTH, calcium/phosphorous, albumin, creatinine, etc.), change in bone mass by densitometry, change in muscle strength in the dominant hand and change in musculoskeletal strength, risk factors for falls, treatment compliance, adverse effects and socio-demographic data.