Osteoporosis: Kendler DL

Lewiecki EM, Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S, Anonymous00044. · New Mexico Clinical Research and Osteoporosis Center, Albuquerque, NM 87106, USA. · South Med J. · Pubmed #18580720 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines for the assessment of skeletal health -- the nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests. Topics are selected for consideration according to criteria that include clinical relevancy, uncertainty in the application of medical evidence to clinical practice, and the likelihood of the expert panel achieving agreement. The most recent Adult PDC was held July 20 to 22, 2007, in Lansdowne, Virginia. Topics included technical and clinical issues relevant to dual-energy x-ray absorptiometry (DXA), vertebral fracture assessment, and bone densitometry technologies other than central DXA. This report describes the methodology and presents the results of this PDC. The first ISCD Pediatric PDC was held June 20 to 21, 2007 in Montreal, Quebec, Canada, and is reported separately.

Khan AA, Hanley DA, Bilezikian JP, Binkley N, Brown JP, Hodsman AB, Josse RG, Kendler DL, Lewiecki EM, Miller PD, Olszynski WP, Petak SM, Syed ZA, Theriault D, Watts NB, Anonymous00369. · Division of Endocrinology, McMaster University, Hamilton, Ontario, Canada, and Hanover General Hospital, PA, USA. · J Clin Densitom. · Pubmed #16731431 No free full text.

Abstract: This document addresses skeletal health assessment in individuals with secondary causes of osteoporosis. Recommendations are based on consensus of the Canadian Panel of the International Society for Clinical Densitometry and invited international experts. Bone mineral density (BMD) testing in these populations is performed in conjunction with careful evaluation of the disease state contributing to bone loss and increased fragility fracture risk, as well as assessment of other contributing risk factors for fracture. The presence of secondary causes of bone loss may further increase the risk of fracture independently of BMD and may necessitate earlier pharmacologic intervention. Dual-energy X-ray absorptiometry is indicated in the initial workup of secondary causes of osteoporosis. The BMD fracture risk relationship is not known for individuals with chronic renal failure (CRF). The BMD testing in this population may be normal in the presence of skeletal fragility, and quantitative bone histomorphometry is better at evaluating skeletal status than BMD in CRF. Dual-energy X-ray absorptiometry is a valuable tool in assessing skeletal health in individuals with secondary causes of osteoporosis.

Binkley N, Bilezikian JP, Kendler DL, Leib ES, Lewiecki EM, Petak SM, Anonymous00364. · University of Wisconsin, Madison, WI, USA. · J Clin Densitom. · Pubmed #16731426 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) convenes a Position Development Conference (PDC) every two years for the purpose of making recommendations on clinically relevant issues in bone densitometry. Topics for consideration are developed by the ISCD Scientific Advisory Committee and the PDC Steering Committee. Clinically relevant questions related to each topic area are assigned to subcommittees for a comprehensive medical literature review and presentation of a report to an international panel of experts. The expert panel includes representatives of the American Society for Bone and Mineral Research (ASBMR) and the International Osteoporosis Foundation (IOF). The recommendations of the PDC expert panel are evaluated by the ISCD Board of Directors, and those that are approved become Official Positions of the ISCD. The Official Positions have subsequently been endorsed by the ASBMR and IOF. The most recent PDC was held July 15-17, 2005, in Vancouver, BC, Canada. Topics considered included technical standardization, vertebral fracture assessment, and application of the 1994 World Health Organization (WHO) criteria to various skeletal sites and to populations other than postmenopausal white women. This report describes the methodology of the 2005 PDC and presents a summary of all ISCD Official Positions.

Khan AA, Bachrach L, Brown JP, Hanley DA, Josse RG, Kendler DL, Leib ES, Lentle BC, Leslie WD, Lewiecki EM, Miller PD, Nicholson RL, O'Brien C, Olszynski WP, Theriault MY, Watts NB, Anonymous00235. · Divisions of Endocrinology and Geriatrics, McMaster University, Hamilton, ON, Canada. · J Clin Densitom. · Pubmed #14742888 No free full text.

Abstract: The Canadian Panel of the International Society for Clinical Densitometry has developed standards in order to establish the minimum level of acceptable performance for the practice of bone densitometry in Canada. Previously, this group addressed the performance of densitometry in postmenopausal women. This report addresses the use of densitometry in men, premenopausal women, and children with a focus on dual-energy X-ray absorptiometry.

Khan AA, Colquhoun A, Hanley DA, Jankowski LG, Josse RG, Kendler DL, Lentle B, Leslie WD, Lewiecki EM, O'neill E, Robertson S, Syed ZA, Tanner SB, Webster D. · Division of Endocrinology, McMaster University, Hamilton, Ontario, Canada. · J Clin Densitom. · Pubmed #17485038 No free full text.

This publication has no abstract.

Blake GM, Lewiecki EM, Kendler DL, Fogelman I. · King's College London School of Medicine, London, UK. · J Clin Densitom. · Pubmed #17485027 No free full text.

Abstract: Strontium ranelate is a new orally administered agent for the treatment of women with postmenopausal osteoporosis that reduces the risk of vertebral and nonvertebral fractures. This review article examines the evidence for the antifracture efficacy and safety of strontium ranelate treatment and discusses the effect of DXA scans, biochemical markers of bone turnover, and bone histology. In the SOTI trial, three years treatment with strontium ranelate led to a 41% reduction in vertebral fracture risk (relative risk [RR]=0.59; 95% CI: 0.48-0.73; p<0.001), while in the TROPOS study there was a 16% reduction in nonvertebral fractures (RR=0.84; 95% CI 0.702-0.995; p=0.04). Compared with alternative osteoporosis therapies, strontium ranelate treated patients show large increases in BMD coupled with comparatively modest changes in biochemical markers of bone turnover and bone histology. While the large BMD changes provide a useful way of monitoring patients' response to treatment, it is important to appreciate that much of the increase is a purely physical effect due to the increased attenuation of X-ray when some of the calcium in bone is replaced by strontium. Strontium ranelate is a useful addition to the range of antifracture treatments available for treating postmenopausal women with osteoporosis and is the only treatment proven to be effective at preventing both vertebral and nonvertebral fractures in women aged 80 yr and older.

Kendler DL. · 120-809 W 41 Ave, Vancouver, British Columbia V5Z 2N6, Canada. · Curr Osteoporos Rep. · Pubmed #16527006 No free full text.

Abstract: Strontium ranelate is a novel therapy for the treatment of postmenopausal osteoporosis with actions to reduce bone resorption and increase bone formation. In vitro, strontium ranelate has anabolic and antiresorptive activity, increasing collagen and non-collagen protein synthesis, enhancing pre-osteoblast differentiation, inhibiting osteoclast differentiation, and reducing osteoclast function. In animal models, the increase in bone density is closely correlated with increases in biomechanical bone strength. Histomorphometry demonstrates reduced osteoclast surfaces with increased bone formation. Clinical trials in postmenopausal women have demonstrated 3-year fracture efficacy. Reductions in vertebral fracture were seen in patients with and without prevalent vertebral fracture. Nonvertebral fractures were also significantly reduced. In a subgroup of patients at high risk for hip fracture, there was a significant reduction in hip fracture risk. Strontium ranelate is well tolerated with nausea, diarrhea, headache, and dermatitis more frequent in treated patients only for the first 3 months of therapy. Together, these data suggest that strontium ranelate is a well-tolerated and effective therapy for postmenopausal osteoporosis reducing vertebral and nonvertebral fracture by a novel dual antiresorptive and anabolic action on bone.

Reginster JY, Felsenberg D, Cooper C, Stakkestad JA, Miller PD, Kendler DL, Adami S, McClung MR, Bolognese MA, Civitelli R, Dumont E, Bonvoisin B, Recker RR, Delmas PD. · Unite d'Exploration du Metabolisme de l'Os et du Cartilage, CHU Centre Ville, Liége, Belgium. · Osteoporos Int. · Pubmed #15959614 No free full text.

Abstract: Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Such regimens require high potency agents, which can be given at low effective doses and that also have good tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats and cynomolgus monkeys. Clinically, a pivotal prospective study has established that oral ibandronate has significant vertebral fracture efficacy in PMO, whether given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months; extended between-dose interval>2 months). Both oral regimens were well tolerated, which is noteworthy as patients with a history of gastrointestinal (GI) disturbance were not specifically excluded. As a result of these findings, a large, multinational, randomized, double-blind study (Monthly Oral iBandronate In LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with proven anti-fracture efficacy, in terms of lumbar spine bone mineral density (BMD) change. As with the trials investigating the weekly administration of other bisphosphonates, vertebral fracture efficacy will be inferred if the study demonstrates the non-inferiority of once-monthly ibandronate to the proven oral daily regimen in terms of spinal BMD change. The availability of this once-monthly ibandronate regimen is expected to offer benefits in terms of convenience (by having to follow dosing recommendations once a month vs. once daily or weekly) and potentially tolerability (by reducing the potential for upper GI irritation that can result from frequent, repeated exposure). Greater convenience and tolerability may enhance the therapy adherence and, hence, improve long-term therapeutic outcomes in PMO.

Hodsman AB, Bauer DC, Dempster DW, Dian L, Hanley DA, Harris ST, Kendler DL, McClung MR, Miller PD, Olszynski WP, Orwoll E, Yuen CK. · University of Western Ontario, St. Joseph's Health Care, Room 2F-15, 268, Grosvenor Street, London, Ontario N6A 4V2, Canada. · Endocr Rev. · Pubmed #15769903 links to  free full text

Abstract: All therapies currently recommended for the management of osteoporosis act mainly to inhibit bone resorption and reduce bone remodeling. PTH and its analog, teriparatide [recombinant human PTH(1-34)], represent a new class of anabolic therapies for the treatment of severe osteoporosis, having the potential to improve skeletal microarchitecture. Significant reductions in both vertebral and appendicular fracture rates have been demonstrated in the phase III trial of teriparatide, involving elderly women with at least one prevalent vertebral fracture before the onset of therapy. However, there is as yet no evidence that the antifracture efficacy of PTH will be superior to the bisphosphonates, whereas cost-utility estimates suggest that teriparatide is significantly more expensive. Teriparatide should be considered as treatment for postmenopausal women and men with severe osteoporosis, as well as for patients with established glucocorticoid-induced osteoporosis who require long-term steroid treatment. Teriparatide should also be considered for the management of individuals at particularly high risk for fractures, including subjects who are younger than age 65 and who have particularly low bone mineral density measurements (T scores < or = 3.5). Teriparatide therapy is not recommended for more than 2 yr, based, in part, on the induction of osteosarcoma in a rat model of carcinogenicity. Total daily calcium intake from both supplements and dietary sources should be limited to 1500 mg together with adequate vitamin D intake (< or =1000 U/d). Monitoring of serum calcium may be safely limited to measurement after 1 month of treatment; mild hypercalcemia may be treated by withdrawing dietary calcium supplements, reducing the dosing frequency of PTH, or both. At present, concurrent therapy with antiresorptive therapy, particularly bisphosphonates, should be avoided, although sequential therapy with such agents may consolidate the beneficial effects upon the skeleton after PTH is discontinued.

Lewiecki EM, Kendler DL, Kiebzak GM, Schmeer P, Prince RL, El-Hajj Fuleihan G, Hans D. · New Mexico Clinical Research & Osteoporosis Center, 300 Oak Street NE, Albuquerque, NM 87106, USA. · Osteoporos Int. · Pubmed #15278247 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines for indications, acquisition, and interpretation of bone density tests. Topics are selected for consideration by the ISCD Scientific Advisory Committee, reviewed by scientific working groups, and presented to an international panel of experts. Topic categories addressed to date include indications for bone density testing, selection of reference databases for T-scores and Z-scores, clinical applications for central and peripheral bone densitometry, serial bone density testing, instrument precision assessment, phantom scanning and calibration testing, requirements for a bone density report, nomenclature, and diagnosis of osteoporosis in postmenopausal women, premenopausal women, men, and children. Following an open session for public comment and discussion, the panel convenes for consideration of each topic and makes recommendations for positions to the ISCD Board of Directors. Recommendations that are accepted become the Official Positions of the ISCD. This Special Report summarizes the methodology of the ISCD PDCs and presents selected Official Positions of general interest.

Papaioannou A, Watts NB, Kendler DL, Yuen CK, Adachi JD, Ferko N. · Department of Medicine, Division of Geriatric Medicine (AP) McMaster University, Hamilton, Ontario, Canada. · Am J Med. · Pubmed #12208381 No free full text.

Abstract: We reviewed the epidemiology, diagnosis, and treatment of vertebral fractures due to osteoporosis in the elderly. Vertebral fractures are underdiagnosed despite their high prevalence in both men and women. Clinical consequences of vertebral fractures include increased risk of future vertebral and hip fracture, acute and chronic back pain, decreased quality of life, and increased mortality. Patients with vertebral fractures have functional impairment and increased mortality similar to those with hip fractures. Asymptomatic fractures identified on radiograph also affect quality of life and mortality. A vertebral fracture is a clinical marker for a subsequent fracture and should trigger assessment and diagnosis of osteoporosis. The care of patients with vertebral fractures includes pain management, rehabilitation, and prevention of further fractures. There is evidence from randomized controlled trials that pharmacologic therapy can reduce the risk of future fractures by 40% to 50%. Vertebroplasty may be effective in the control of pain and in obtaining stability of the spine.

Drake WM, Kendler DL, Brown JP. · Department of Medicine, University of British Columbia, Vancouver, Canada. · Clin Ther. · Pubmed #11354395 No free full text.

Abstract: BACKGROUND: Bisphosphonate therapy remains the most effective way of controlling Paget's disease of bone (PD). Along with salmon calcitonin, etidronate has been the mainstay of therapy for approximately 20 years. However, the advent of newer bisphosphonates with different molecular actions on osteoclasts warrants a reevaluation of optimal treatment. OBJECTIVE: At a symposium of the Western Osteoporosis Alliance, physicians with experience in the management of PD met to review currently available information and generate this consensus statement as a guideline for clinicians and a source of information for health care payers. METHODS: All available randomized, double-blind, controlled studies that compared the efficacy of newer bisphosphonates with that of etidronate in the treatment of PD were identified through a search of MEDLINE using the terms Paget's disease, bisphosphonates, pamidronate, etidronate, alendronate, risedronate, tiludronate, clodronate, calcitonin, and salmon calcitonin. Because no such studies have been conducted for pamidronate, clodronate, or calcitonin, these drugs were not included in the analysis. CONCLUSIONS: The consensus of the symposium was that etidronate has little place in the modern management of PD. Newer bisphosphonates such as alendronate and risedronate provide significant therapeutic advantages over etidronate, both in the extent of reduction in bone-specific alkaline phosphatase (BSAP) and/or total serum alkaline phosphatase (SAP) and in the duration of remission, as measured by normalization of BSAP/SAP. In the absence of a direct comparison between alendronate and risedronate in the treatment of PD, physician choice is likely to be based on personal experience, relative cost, and differences in dosing.

Adachi JD, Olszynski WP, Hanley DA, Hodsman AB, Kendler DL, Siminoski KG, Brown J, Cowden EA, Goltzman D, Ioannidis G, Josse RG, Ste-Marie LG, Tenenhouse AM, Davison KS, Blocka KL, Pollock AP, Sibley J. · Department of Medicine, St Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada. · Semin Arthritis Rheum. · Pubmed #10707991 No free full text.

Abstract: OBJECTIVES: To educate scientists and health care providers about the effects of corticosteroids on bone, and advise clinicians of the appropriate treatments for patients receiving corticosteroids. METHODS: This review summarizes the pathophysiology of corticosteroid-induced osteoporosis, describes the assessment methods used to evaluate this condition, examines the results of clinical trials of drugs, and explores a practical approach to the management of corticosteroid-induced osteoporosis based on data collected from published articles. RESULTS: Despite our lack of understanding about the biological mechanisms leading to corticosteroid-induced bone loss, effective therapy has been developed. Bisphosphonate therapy is beneficial in both the prevention and treatment of corticosteroid-induced osteoporosis. The data for the bisphosphonates are more compelling than for any other agent. For patients who have been treated but continue to lose bone, hormone replacement therapy, calcitonin, fluoride, or anabolic hormones should be considered. Calcium should be used only as an adjunctive therapy in the treatment or prevention of corticosteroid-induced bone loss and should be administered in combination with other agents. Conclusions: Bisphosphonates have shown significant treatment benefit and are the agents of choice for both the treatment and prevention of corticosteroid-induced osteoporosis.

Bone HG, Bolognese MA, Yuen CK, Kendler DL, Wang H, Liu Y, San Martin J. · Michigan Bone and Mineral Clinic, 22201 Moross Road, Detroit, MI 48236, USA. · J Clin Endocrinol Metab. · Pubmed #18381571 links to  free full text

Abstract: CONTEXT: Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, a mediator of osteoclastogenesis and osteoclast survival. OBJECTIVE: This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD. DESIGN AND SETTING: This 2-yr randomized, double-blind, placebo-controlled study was conducted in North America. PARTICIPANTS: Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between -1.0 and -2.5. Interventions: SUBJECTS were randomly assigned to receive denosumab sc, 60 mg every 6 months, or placebo. Randomization was stratified by time since onset of menopause (< or =5 yr or > 5 yr). MAIN OUTCOME MEASURES: The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months. Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography; percent change in BMD by dual-energy x-ray absorptiometry for the total hip, one-third radius, and total body; hip structural analysis; percent change in BTMs; and safety. RESULTS: Denosumab significantly increased lumbar spine BMD, compared with placebo at 24 months (6.5 vs. -0.6%; P<0.0001) with similar results for both strata. Denosumab also produced significant increases in BMD at the total hip, one-third radius, and total body (P < 0.0001 vs. placebo); increased distal radius volumetric BMD (P < 0.01); improved hip structural analysis parameters; and significantly suppressed serum C-telopeptide, tartrate-resistant acid phosphatase-5b, and intact N-terminal propeptide of type 1 procollagen. The overall incidence of adverse events was similar between both study groups. CONCLUSIONS: Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women.

Miller PD, McClung MR, Macovei L, Stakkestad JA, Luckey M, Bonvoisin B, Reginster JY, Recker RR, Hughes C, Lewiecki EM, Felsenberg D, Delmas PD, Kendler DL, Bolognese MA, Mairon N, Cooper C. · Colorado Center for Bone Research, Lakewood, Colorado, USA. · J Bone Miner Res. · Pubmed #16007327 No free full text.

Abstract: Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year. INTRODUCTION: Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis. Although yet to be prospectively shown in osteoporosis, evidence from randomized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence. Ibandronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of >2 months. This report presents comparative data on the efficacy and safety of monthly and daily oral ibandronate regimens. MATERIALS AND METHODS: MOBILE is a 2-year, randomized, double-blind, phase III, noninferiority trial. A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ibandronate regimens: 2.5 mg daily, 50 mg/50 mg monthly (single doses, consecutive days), 100 mg monthly, or 150 mg monthly. RESULTS: After 1 year, lumbar spine BMD increased by 3.9%, 4.3%, 4.1%, and 4.9% in the 2.5, 50 /50, 100, and 150 mg arms, respectively. All monthly regimens were proven noninferior, and the 150 mg regimen superior, to the daily regimen. All monthly regimens produced similar hip BMD gains, which were larger than those with the daily regimen. All regimens similarly decreased serum levels of C-telopeptide, a biochemical marker of bone resorption. Compared with the daily regimen, a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine (6%) or total hip BMD (3%). All regimens were similarly well tolerated. CONCLUSIONS: Monthly ibandronate is at least as effective and well tolerated as the currently approved daily ibandronate regimen in postmenopausal osteoporosis.

Brown JP, Kendler DL, McClung MR, Emkey RD, Adachi JD, Bolognese MA, Li Z, Balske A, Lindsay R. · Le Centre de recherche du CHUL, Laval University, Sainte-Foy, Québec, Canada. · Calcif Tissue Int. · Pubmed #12085156 No free full text.

Abstract: This study evaluated the efficacy and tolerability of risedronate once a week (35 mg and 50 mg) compared with risedronate 5 mg once daily in women with osteoporosis. We conducted a randomized, double-blind, active-controlled, 2-year study; the primary efficacy assessment was performed after 1 year. Subjects were women aged 50 years or older who had been postmenopausal for at least 5 years, with either a bone mineral density (BMD) T-score of -2.5 or lower (lumbar spine or proximal femur) or a T-score lower than -2 and at least one prevalent vertebral fracture. Subjects received risedronate 5 mg once daily, 35 mg once a week or 50 mg once a week. All subjects also received 1 g daily of elemental calcium supplementation and supplemental vitamin D if the baseline serum levels were low. The primary efficacy measure was percent change in lumbar spine BMD at 12 months. A total of 1,456 women were randomized and received medication; 1,209 (83%) women completed 12 months. The mean percent change (SE) in lumbar spine BMD after 12 months was 4.0% (0.2%) in the 5 mg daily group, 3.9% (0.2%) in the 35 mg group, and 4.2% (0.2%) in the 50 mg group; each once-a-week treatment was determined to be as effective as the daily treatment. Outcomes of the secondary efficacy measurements and safety assessments were also similar in all 3 groups after 12 months. Risedronate 35 mg and 50 mg once a week provide the same efficacy and safety as the daily 5 mg regimen; therefore, the lower dose, 35 mg once a week, is considered optimal for women with postmenopausal osteoporosis who desire a once-a-week regimen.

Drake WM, Brown JP, Banville C, Kendler DL. · Osteoporosis Research Center, University of British Columbia, Vancouver, Canada. · Osteoporos Int. · Pubmed #11991446 No free full text.

Abstract: In women with postmenopausal osteoporosis (PMO), response to therapy with bisphosphonates is conventionally monitored using central-site (hip and spine) bone mineral density (BMD), but more convenient alternatives are desirable. During a randomized parallel-group study of the efficacy of once-weekly (80 mg vs 160 mg) oral alendronate in the treatment of PMO, 81 women (mean age 70.2 years +/- 4.6 SD) had BMD measurements of total hip (TH) and lumbar spine (LS) (L1-L4, Hologic); and of the middle phalanx of the middle digit of the non-dominant hand (accuDXA) at baseline and after 6 and 12 months of therapy with alendronate. At the same timepoints, subjects also had measurements of speed of sound (SOS) through bone at four sites (distal 1/3 radius, proximal phalanx of the third finger, midshaft of the tibia and fifth metatarsal) using the Sunlight Omnisense Ultrasound Bone Sonometer. Data from both patient groups were pooled for this analysis. Mean TH BMD at baseline was 0.705 g/cm2 +/- 0.093 (SD) and increased by 1.7% +/- 2.3% and 2.5% +/- 2.3% at 6 and 12 months respectively (p = 0.09 and p<0.0001). Mean LS BMD at baseline was 0.718 +/- 0.076 g/cm2 and increased by 3.9% +/- 3.6% and 6.1% +/- 3.5% at 6 and 12 months respectively (both p<0.0001). There was no statistically significant change from baseline in mean BMD by accuDXA at either 6 or 12 months. The only statistically significant changes in SOS were at the radius (decrease in SOS at 12 months, p= 0.04) and tibia (increase at 6 months, p<0.01, but no change between baseline and 12 months). Baseline correlation coefficients between accuDXA and LS and TH DXA were 0.22 (p = 0.05) and 0.27 (p = 0.02) respectively. Correlation coefficients between SOS and LS DXA ranged from 0.05 to 0.22; and between SOS and TH DXA ranged from -0.08 to 0.10 (all p = NS). These data suggest that the response to alendronate therapy over this time period cannot be measured by accuDXA or Sunlight SOS at the sites studied.

Adachi JD, Adami S, Miller PD, Olszynski WP, Kendler DL, Silverman SL, Licata AA, Li Z, Gomez-Panzani E. · Department of Medicine, St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada, · Aging (Milano). · Pubmed #11820707 No free full text.

Abstract: Bisphosphonates are effective treatments for osteoporosis, but some have been associated with upper gastrointestinal intolerance. This randomized, double-blind study assessed the upper gastrointestinal tolerability of risedronate in postmenopausal women who had discontinued alendronate treatment because of upper gastrointestinal adverse events. Sixty-six women who had previously discontinued treatment with alendronate 10 mg/day because of upper gastrointestinal symptoms received placebo (N=31) or risedronate 5 mg (N=35) daily for 3 months. The primary outcome was the rate of discontinuation due to upper gastrointestinal adverse events: 5/31 (16.1%) in the placebo group, and 4/35 (11.4%) in the risedronate group. Discontinuation rates were also similar in the two treatment groups among subgroups of patients with a history of gastrointestinal disorder, prior use of acid suppression drugs, and concomitant use of NSAIDs. The overall incidence of upper gastrointestinal events was comparable between the placebo (19.4%) and risedronate (20.0%) groups. Overall, risedronate 5 mg/day for 3 months was as well tolerated as placebo in patients who could not tolerate alendronate 10 mg. These results are consistent with, and complement those from previous studies showing that risedronate 5 mg has a gastrointestinal tolerability similar to that of placebo.

Brown JP, Olszynski WP, Hodsman A, Bensen WG, Tenenhouse A, Anastassiades TP, Ste-Marie LG, Kendler DL, Hanley DA, Josse R, Hanly JG, Lentle B, Jovaisas A, Ioannidis G, Stephenson GF, Barton I, Pack S, Chines A, Dias R, Adachi JD. · Centre de Recherche du CHUL, Centre Hospitalier Universitaire de Quebec, 2705 boul Laurier #S-784, Ste-Foy, Québec, G1V 4G2 Canada. · J Clin Densitom. · Pubmed #11748341 No free full text.

Abstract: Following a 52-wk randomized controlled trial of intermittent cyclic etidronate therapy in patients using corticosteroids, we performed a 52-wk open-label trial of calcium alone in 114 corticosteroid-treated patients to determine whether the beneficial effect of etidronate is maintained after the drug is discontinued. All patients were given 500 mg/d of elemental calcium. Sixty-one and 53 patients made up the former placebo and etidronate groups, respectively. A total of 89 (98%) of patients in the former placebo and etidronate groups remained on corticosteroids throughout the second year. The mean (SE) percentage change in bone mineral density of the lumbar spine, femoral neck, and trochanter were compared between groups. The difference between groups in mean percentage change from baseline (wk 0, initiation of etidronate or placebo therapy) in the bone density of the lumbar spine, femoral neck, and trochanter, following 104 wk, was 3.8 (0.9), 3.0 (1.1), and 4.3 (1.1), respectively (p < 0.05, all sites), in favor of the former etidronate group. While not significant, the former placebo group demonstrated a slightly larger rate of decline in bone density over the second year than the former etidronate group at all three sites. Following the discontinuation of etidronate therapy, there was no accelerated bone loss and there was evidence of a residual protective effect in both the lumbar spine and femoral neck for up to 1 yr posttreatment.

Rittmaster RS, Bolognese M, Ettinger MP, Hanley DA, Hodsman AB, Kendler DL, Rosen CJ. · Department of Medicine and the Queen Elizabeth II Health Sciences Center, Dalhousie University, Halifax, Nova Scotia, Canada. · J Clin Endocrinol Metab. · Pubmed #10852440 links to  free full text

Abstract: Treatment of osteoporosis with PTH causes a marked increase in vertebral bone mineral density (BMD). However, this effect is rapidly reversed when the treatment is stopped. The purpose of the present study was to determine whether the bisphosphonate alendronate could preserve or enhance bone density in patients previously treated with PTH. Sixty-six postmenopausal osteoporotic women were treated for 1 yr with 50, 75, or 100 microg recombinant human PTH-(1-84) or placebo, and then were given 10 mg alendronate daily for an additional year. BMD was measured in the femoral neck, lumbar spine, and whole body. Markers of bone turnover included skeletal alkaline phosphatase, osteocalcin, and N-telopeptide. During the first year, changes in BMD (mean +/- SD) in women receiving PTH (all doses combined) were 7.1 +/- 5.6% (spine), 0.3 +/- 6.2% (femoral neck), and -2.3 +/- 3.3% (total body). After switching to alendronate for 1 yr in women who previously had received PTH, mean changes in BMD were 13.4 +/- 6.4% (spine), 4.4 +/- 7.2% (femoral neck), and 2.6 +/- 3.1% (whole body). In the subgroup of patients who had received the highest dose of PTH, the mean increase in vertebral BMD was 14.6 +/- 7.9%. All markers of bone turnover increased during treatment with PTH and decreased to below baseline after 1 yr of alendronate. In conclusion, sequential treatment of osteoporosis with PTH and alendronate results in an increase in vertebral bone density that is considerably more than has been reported with alendronate or estrogens alone. This combination of drugs may be a useful approach to maximizing bone density in women with vertebral osteoporosis.

Kendler DL, Adachi JD, Josse RG, Slosman DO. · University of British Columbia, Vancouver, BC, Canada. · Osteoporos Int. · Pubmed #19266136 No free full text.

Abstract: PURPOSE: The purpose of this study was to review the monitoring of strontium ranelate osteoporosis therapy. METHODS: The method used in this study was comprehensive literature review with clinical perspectives. RESULTS: Changes in bone turnover markers (BTM) or bone mineral density (BMD) have been documented in osteoporosis clinical trials. However, neither BMD nor BTM changes fully explain the observed fracture risk reduction in treated patients. If changes in BMD or BTM on therapy would be easily discernable in individual patients, and were strongly associated with fracture risk reduction, monitoring individuals would be more useful. BMD changes in patients on strontium ranelate are of a greater magnitude and hence can be easily determined in an individual patient. In addition, there exists a better correlation between fracture risk reduction and increases in BMD. CONCLUSIONS: The strong correlation between measured BMD increases and fracture risk reduction in patients on strontium ranelate therapy will be of clinical benefit to physicians wishing to evaluate both treatment persistence and fracture risk reduction.

Lewiecki EM, Gordon CM, Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S, Bishop NJ, Leonard MB, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS. · New Mexico Clinical Research & Osteoporosis Center, 300 Oak Street NE, Albuquerque, NM 87106, USA. · Osteoporos Int. · Pubmed #18633664 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) conducts Position Development Conferences (PDCs) for the purpose of establishing standards and guidelines in the field of bone densitometry. Topics for consideration are selected according to clinical relevance, a perceived need for standardization, and the likelihood of achieving agreement. Questions regarding nomenclature, indications, acquisition, analysis, quality control, interpretation, and reporting of bone density tests for each topic area are assigned to task forces for a comprehensive review of the scientific literature. The findings of the review and recommendations are then presented to an international panel of experts at the PDC. The expert panel votes on potential Official Positions for appropriateness, necessity, quality of the evidence, strength of the recommendation, and applicability (worldwide or variable according to local requirements). Recommendations that are approved by the ISCD Board of Directors become Official Positions. The first Pediatric PDC was 20-21 June 2007 in Montreal, QC, Canada. The most recent Adult PDC was held 20-22 July 2007, in Lansdowne, VA, USA. This Special Report summarizes the methodology of the ISCD PDCs and presents selected Official Positions of general interest.

Chen P, Miller PD, Binkley NC, Kendler DL, Wong M, Krohn K. · Eli Lilly and Company, Indianapolis, IN, USA. · J Clin Densitom. · Pubmed #18599331 No free full text.

Abstract: For diagnosing osteoporosis, International Society for Clinical Densitometry guidelines suggest using the lowest bone mineral density T-score of the lumbar spine (LS), femoral neck (FN), or total hip (TH). For the LS, use of the total spine (L1-L4) T-score is suggested. Although controversial, some authors have suggested using a single lumbar vertebra of L1-L4 with the lowest T-score to diagnose osteoporosis. We compared the ability of various T-score approaches [lowest single LS vertebra of L1-L4; total spine; FN; TH; and the lowest T-score of total spine, FN, or TH to diagnose osteoporosis in 2560 postmenopausal women from the Multiple Outcomes of Raloxifene Evaluation trial placebo group. The discriminatory ability of each T-score approach to identify women with or without vertebral fracture was compared using the area under receiver-operating characteristic curve. When the lowest single LS T-score of L1-L4 and the total spine T-score were used, 77% and 57% of women were categorized as having osteoporosis, respectively. These T-score approaches had similar ability for discriminating between women with or without prevalent vertebral fractures and for predicting the risk of incident vertebral fractures. The lowest single LS vertebra T-score identified a greater proportion of women with osteoporosis than currently accepted approaches. Thus, the WHO diagnostic classification should not be applied to single vertebral T-scores. This analysis supports the current International Society for Clinical Densitometry position to use the total spine T-score for osteoporosis diagnosis.

Simonelli C, Adler RA, Blake GM, Caudill JP, Khan A, Leib E, Maricic M, Prior JC, Eis SR, Rosen C, Kendler DL. · HealthEast Osteoporosis Care, St. Paul, MN, USA. <> · J Clin Densitom. · Pubmed #18442756 No free full text.

Abstract: At the 2007 Position Development Conference, the Dual-Energy X-ray Absorptiometry Technical Task Force investigated three major areas of bone density testing. Although bone mineral density (BMD) testing in men had previously been reviewed at the 2005 Position Development Conference, we reviewed the most recent data in men to develop appropriate indications for bone density testing in men. We continue to recommend screening at age 70 and discuss the clinical risk factors that may be an appropriate indication for earlier BMD testing. Menopausal transition (perimenopause) was considered an important time to consider BMD evaluation because bone loss may be significant prior to menopause. However, because fracture risk is inherently low in women of this age without other risk factors, screening BMD testing is not appropriate. We discuss the risk factors that are strong indicators of fracture risk that may be increased during the menopause transition. The presence of these risk factors are appropriate indications for BMD testing with applicability of WHO diagnostic categorization. The issue of establishing a high threshold for BMD was investigated thoroughly and the current literature was reviewed. Despite the fact there is agreement that all BMD values greater than T-score -1.0 are not normal, it was felt that because of the paucity of sensitivity data and confounding factors such as high body mass index, an upper threshold could not be established or recommended at this time. This was felt to be an important area for further research.

Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Lewiecki EM, Silverman S. · Medical College of Wisconsin, Milwaukee, WI, USA. <> · J Clin Densitom. · Pubmed #18442754 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) convenes a Position Development Conference (PDC) every 2 yr to make recommendations for standards in the field of bone densitometry. The recommendations are based on clinically relevant issues in bone densitometry such as quality control, acquisition, analysis, interpretation and reporting. Topics for consideration are developed by the ISCD Board of Directors and its Scientific Advisory Committee. Clinically relevant questions related to each topic area are assigned to task forces for a comprehensive review of the medical literature and subsequent presentation of the reports to an international panel of experts. For this PDC, the Expert Panel included representatives of the American Society for Bone and Mineral Research, International Bone and Mineral Society and the National Osteoporosis Foundation. The recommendations of the PDC Expert Panel are then reviewed by the ISCD Board of Directors. Recommendations that are approved become Official Positions of the ISCD. The most recent PDC was held July 20-22, 2007, in Lansdowne, Virginia, USA. Topics considered included vertebral fracture assessment, technical and clinical issues relevant to dual-energy X-ray absorptiometry (DXA), and bone densitometry technologies other than central DXA. This report describes the methodology and the results of the Lansdowne, Virginia, USA 2007 PDC, and a summary of all ISCD Official Positions, including the ones recently adopted by this PDC and the 2007 Pediatric PDC held in Montreal, Quebec, Canada.