Recurrent vesical calculi, hypercalciuria, and biochemical evidence of increased bone resorption in an adult male with paraplegia due to spinal cord injury: is there a role for intermittent oral disodium etidronate therapy for prevention of calcium phosphate bladder stones?

Study design: Clinical case report with comments by colleagues from Sweden, Poland, Spain, Brazil, Japan, Belgium and Switzerland.Objectives: To discuss the role of disodium etidronate therapy for prevention of calcium phosphate vesical calculi in persons with spinal cord injury, who have hypercalciuria and biochemical evidence of increased bone resorption.Setting: Regional Spinal Injuries Centre, Southport, UK.Methods: A 21-year-old male sustained paraplegia (T-10; ASIA scale: A) in a road traffic accident in June 2001. He had an indwelling urethral catheter until the end of August 2001, when he started self-catheterisation. He developed bladder stones and electrohydraulic lithotripsy (EHL) was performed in May 2002. All stone fragments were removed. Recurrence of vesical calculi was noted in October 2002. These stones were fragmented by lithoclast lithotripsy in two sessions, in December 2002 and February 2003; all stone fragments were removed at the end of the second session. This patient reverted to indwelling catheter drainage when vesical calculi recurred. in September 2003, X-ray of the abdomen showed recurrence of vesical calculi. By February 2004, the stones had increased in size and number. EHL of vesical calculi was again performed in April 2004. Complete clearance was achieved.Results: A 24-h urinalysis detected hypercalciuria - 18.7 mmol/day ( reference range: 2.5 - 7.5). Biochemical analysis of vesical calculus revealed calcium phosphate (85%) and magnesium ammonium phosphate (15%). Plasma C-terminal telopeptide (CTX) was increased - 1.06 ng/ml ( reference range: 0.1 - 0.5 ng/ml). Free deoxypyridinoline/creatinine ratio (fDPD/Cr) in urine was also increased - 20.2 ( reference range: 2.3 - 5.4). in April 2004, this patient was prescribed disodium etidronate 400 mg day. Nearly 3 months after commencing therapy with etidronate, plasma CTX decreased to 0.87 ng/ml. fDPD/Cr in urine also decreased to 12.4. After 4 months of etidronate therapy, 24- h urinary calcium excretion had decreased to 6.1 mmol/day.Conclusion: Etidronate ( 400 mg daily) is a very effective inhibitor of calcium phosphate crystallisation. Etidronate decreased urinary excretion of calcium, an important factor in prevention of calcium phosphate bladder stones. Etidronate therapy is not a substitute for other well-established methods for prevention of vesical calculi in spinal cord injury patients, for example, large fluid intake, avoiding long-term catheter drainage. Intermittent therapy with etidronate may be considered in selected patients, in whom hypercalciuria persists after instituting nonpharmacological therapy for an adequate period, for example, early mobilisation, weight-bearing exercises, and functional electrical stimulation. However, possible side effects of etidronate, and the fact that etidronate is not licensed in United Kingdom for prevention of urolithiasis, should be borne in mind.Dist Gen Hosp, Reg Spinal Injuries Ctr, Southport, EnglandDist Gen Hosp, Dept Biochem, Southport, EnglandSahlgrenska Univ Hosp, Dept Urol, Gothenburg, SwedenMetropolitan Rehabil Ctr, Dept Neurourol, Konstancin, PolandUniv Balearic Isl, Inst Hlth Sci Res IUNICS, Lab Renal Lithiasis Res, Palma de Mallorca, SpainUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilNagoya City Univ, Grad Sch Med Sci, Dept Nephrourol, Nagoya, Aichi, JapanUniv Ziekenhuis Antwerpen, Cent Urol Revalidatie, Edegem, BelgiumUniv Hosp Balgrist, Spinal Cord Injury Ctr, Dept Neurourol, Zurich, SwitzerlandDist Gen Hosp, Dept Radiol, Southport, EnglandRoyal Liverpool & Broadgreen Univ Hosp, Dept Clin Chem, Liverpool, Merseyside, EnglandUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilWeb of Scienc

From space to Earth: advances in human physiology from 20 years of bed rest studies (1986–2006)

Bed rest studies of the past 20 years are reviewed. Head-down bed rest (HDBR) has proved its usefulness as a reliable simulation model for the most physiological effects of spaceflight. As well as continuing to search for better understanding of the physiological changes induced, these studies focused mostly on identifying effective countermeasures with encouraging but limited success. HDBR is characterised by immobilization, inactivity, confinement and elimination of Gz gravitational stimuli, such as posture change and direction, which affect body sensors and responses. These induce upward fluid shift, unloading the body’s upright weight, absence of work against gravity, reduced energy requirements and reduction in overall sensory stimulation. The upward fluid shift by acting on central volume receptors induces a 10–15% reduction in plasma volume which leads to a now well-documented set of cardiovascular changes including changes in cardiac performance and baroreflex sensitivity that are identical to those in space. Calcium excretion is increased from the beginning of bed rest leading to a sustained negative calcium balance. Calcium absorption is reduced. Body weight, muscle mass, muscle strength is reduced, as is the resistance of muscle to insulin. Bone density, stiffness of bones of the lower limbs and spinal cord and bone architecture are altered. Circadian rhythms may shift and are dampened. Ways to improve the process of evaluating countermeasures—exercise (aerobic, resistive, vibration), nutritional and pharmacological—are proposed. Artificial gravity requires systematic evaluation. This review points to clinical applications of BR research revealing the crucial role of gravity to health