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Geeta Hampson,1,2 Ignac Fogelman1,31Osteoporosis Screening Unit, Guy’s Hospital, 2Department of Chemical Pathology, St Thomas’ Hospital, 3Department of Nuclear Medicine, Guy’s Hospital, London, UKAbstract: Bisphosphonates (BPs) are synthetic analogues of pyrophosphate. They inhibit bone resorption and are therefore widely used in disorders where there are increases or disruptions in bone resorption. This includes postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, Paget’s disease of bone, and malignancy-related bone loss. To best understand the clinical application of BPs, an understanding of their pharmacokinetics and pharmacodynamics is important. This review describes the structure, pharmacology and mode of action of BPs, focusing on their role in clinical practice. Controversies and side effects surrounding their use will also be discussed.Keywords: pyrophosphate, bone resorption, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, Paget’s disease of bone, malignancy-related bone loss

Byline: R. P. Heaney (1), T. M. Zizic (2), I. Fogelman (3), W. P. Olszynski (4), P. Geusens (5), C. Kasibhatla (6), N. Alsayed (6), G. Isaia (7), M. W. Davie (8), C. H. Chesnut III (9) Keywords: Key words:Bone mineral density -- Osteoporosis -- Risedronate -- Vertebral fracture Abstract: Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =--3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90% P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90% P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96% P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Author Affiliation: (1) Creighton University, Omaha, Nebraska, USA, US (2) Chesapeake Medical Research, Baltimore, Maryland, USA, US (3) Guy's Hospital, London, UK, GB (4) Midtown Medical Center, Saskatoon, Saskatchewan, Canada, CA (5) Limburg University Center, Diepenbeek, Belgium, and University Hospital, Maastricht, The Netherlands, NL (6) Procter &amp Gamble Pharmaceuticals, Cincinnati, Ohio, USA, US (7) University of Turin, Turin, Italy, IT (8) Charles Salt Centre, Oswestry, Shropshire, UK , GB (9) University of Washington, Seattle, Washington, USA, US Article note: Received: 12 September 2001 / Accepted: 11 December 2001

Byline: R. Patel (1), D. Collins (2), S. Bullock (1), R. Swaminathan (3), G. M. Blake (1), I. Fogelman (1) Keywords: Key words:Bone density -- Bone markers -- Seasonal variation -- Vitamin D Abstract: Vitamin D status is known to be an important determinant of bone mineral density (BMD). There is a significant seasonal variation in serum vitamin D, and some studies have reported an associated seasonal variation in BMD. The present study was devised to investigate whether a seasonal variation in BMD could be detected in healthy normal subjects, along with associated variations in serum parathyroid hormone (PTH), intestinal calcium absorption and biochemical markers of bone turnover. A second aim was to investigate whether, if such variations were identified, they could be suppressed by vitamin D supplementation. The subjects were 70 healthy female volunteers (mean age 47.2 years, range 24--70 years) recruited into a double-masked crossover study and followed over 2 years. During the first year 35 subjects received a daily oral supplement containing 800 IU (20 mg) cholecalciferol (group 1) and 35 subjects received a placebo preparation (group 2). During the second year the treatment each group received was reversed. Lumbar spine (L1--L4), left proximal femur and total body BMD were measured by DXA at 3-month intervals. Serum 25-hydroxyvitamin D (25-OHD), serum PTH, bone markers (bone-specific ALP (BSAP) and urinary crosslinks (DYPD/creatinine)) and calcium absorption were also measured at each visit. Cholecalciferol treatment increased serum 25-OHD by 25.4 nmol/l (p &lt 0.001), while a reciprocal decrease in serum PTH of 6.6 ng/l (p=0.011) was seen in subjects in the lowest quartile of baseline serum 25-OHD. The treatment had no significant effect on spine, femur or total body BMD, calcium absorption or bone markers. When Fourier analysis was used to analyze the data for seasonal effect (defined as twice the amplitude of the 1-year period variation) a highly significant effect for 25-OHD of 18 nmol/l (p &lt 0.001) was found. However, no effect was found for BMD, PTH, calcium absorption or bone markers. The analysis set a 95% confidence limit to the seasonal effect of less than 0.6% for spine, total hip and total body BMD. It was concluded that in the population of healthy women studied there was no evidence of seasonal variation in spine, femur or total body BMD, serum PTH, calcium absorption or bone markers. Vitamin D supplementation was found to have no effect on BMD. Author Affiliation: (1) Department of Nuclear Medicine, Guy's Hospital, London, GB (2) Department of Chemical Pathology, Hemel Hempstead General Hospital, Herts , GB (3) Department of Clinical Chemistry, Guy's Hospital, London, UK, GB Article note: Received: 7 July 2000 / Accepted: 14 November 2000