Osteoporosis: Kendler D

Khan AA, Sándor GK, Dore E, Morrison AD, Alsahli M, Amin F, Peters E, Hanley DA, Chaudry SR, Dempster DW, Glorieux FH, Neville AJ, Talwar RM, Clokie CM, Al Mardini M, Paul T, Khosla S, Josse RG, Sutherland S, Lam DK, Carmichael RP, Blanas N, Kendler D, Petak S, St-Marie LG, Brown J, Evans AW, Rios L, Compston JE, Anonymous00076. · Divisions of Endocrinology and Geriatrics, McMaster University, Hamilton, Ontario, Canada. · J Rheumatol. · Pubmed #18528958 No free full text.

Abstract: OBJECTIVE: Following publication of the first reports of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates in 2003, a call for national multidisciplinary guidelines based upon a systematic review of the current evidence was made by the Canadian Association of Oral and Maxillofacial Surgeons (CAOMS) in association with national and international societies concerned with ONJ. The purpose of the guidelines is to provide recommendations regarding diagnosis, identification of at-risk patients, and prevention and management strategies, based on current evidence and consensus. These guidelines were developed for medical and dental practitioners as well as for oral pathologists and related specialists. METHODS: The multidisciplinary task force established by the CAOMS reviewed all relevant areas of research relating to ONJ associated with bisphosphonate use and completed a systematic review of current literature. These evidence-based guidelines were developed utilizing a structured development methodology. A modified Delphi consensus process enabled consensus among the multidisciplinary task force members. These guidelines have since been reviewed by external experts and endorsed by national and international medical, dental, oral surgery, and oral pathology societies. RESULTS: Recommendations regarding diagnosis, prevention, and management of ONJ were made following analysis of all current data pertaining to this condition. ONJ has many etiologic factors including head and neck irradiation, trauma, periodontal disease, local malignancy, chemotherapy, and glucocorticoid therapy. High-dose intravenous bisphosphonates have been identified as a risk factor for ONJ in the oncology patient population. Low-dose bisphosphonate use in patients with osteoporosis or other metabolic bone disease has not been causally linked to the development of ONJ. Prevention, staging, and treatment recommendations are based upon collective expert opinion and current data, which has been limited to case reports, case series, surveys, retrospective studies, and 2 prospective observational studies. Recommendations: In all oncology patients, a thorough dental examination including radiographs should be completed prior to the initiation of intravenous bisphosphonate therapy. In this population, any invasive dental procedure is ideally completed prior to the initiation of high-dose bisphosphonate therapy. Non-urgent procedures are preferably delayed for 3 to 6 months following interruption of bisphosphonate therapy. Osteoporosis patients receiving oral or intravenous bisphosphonates do not require a dental examination prior to initiating therapy in the presence of appropriate dental care and good oral hygiene. Stopping smoking, limiting alcohol intake, and maintaining good oral hygiene should be emphasized for all patients receiving bisphosphonate therapy. Individuals with established ONJ are most appropriately managed with supportive care including pain control, treatment of secondary infection, removal of necrotic debris, and mobile sequestrate. Aggressive debridement is contraindicated. CONCLUSION: Our multidisciplinary guidelines, which provide a rational evidence-based approach to the diagnosis, prevention, and management of bisphosphonate-associated ONJ in Canada, are based on the best available published data and the opinion of national and international experts involved in the prevention and management of ONJ.

Khan AA, Brown J, Faulkner K, Kendler D, Lentle B, Leslie W, Miller PD, Nicholson L, Olszynski WP, Watts NB, Anonymous00159. · McMaster University, Oakville, Ontario, Canada. · J Clin Densitom. · Pubmed #12665644 No free full text.

Abstract: The International Society for Clinical Densitometry (ISCD) is a multidisciplinary nonprofit global organization formed to ensure excellence in densitometry imaging, interpretation, and application. The Canadian panel of the ISCD represents ISCD in Canada and oversees Canadian bone densitometry certification programs. The standards of care from the Canadian panel of the ISCD have been developed in order to establish the minimum level of acceptable performance for the practice of bone densitometry in Canada. A variety of techniques are available for skeletal assessment of bone mineral density, which vary in accuracy, precision, and clinical utility as well as availability. This article focuses on central dual X-ray absorptiometry in adults and does not address densitometry in the pediatric population. Other technologies will be addressed in a subsequent article.

Khan AA, Sándor GK, Dore E, Morrison AD, Alsahli M, Amin F, Peters E, Hanley DA, Chaudry SR, Lentle B, Dempster DW, Glorieux FH, Neville AJ, Talwar RM, Clokie CM, Mardini MA, Paul T, Khosla S, Josse RG, Sutherland S, Lam DK, Carmichael RP, Blanas N, Kendler D, Petak S, Ste-Marie LG, Brown J, Evans AW, Rios L, Compston JE, Anonymous00115. · Divisions of Endocrinology and Geriatrics, McMaster University, Oakville, ON L6J 1X8, Canada. · J Rheumatol. · Pubmed #19286860 No free full text.

Abstract: In 2003, the first reports describing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BP) were published. These cases occurred in patients with cancer receiving high-dose intravenous BP; however, 5% of the cases were in patients with osteoporosis receiving low-dose bisphosphonate therapy. We present the results of a systematic review of the incidence, risk factors, diagnosis, prevention, and treatment of BP associated ONJ. We conducted a comprehensive literature search for relevant studies on BP associated ONJ in oncology and osteoporosis patients published before February 2008.All selected relevant articles were sorted by area of focus. Data for each area were abstracted by 2 independent reviewers. The results showed that the diagnosis is made clinically. Prospective data evaluating the incidence and etiologic factors are very limited. In oncology patients receiving high-dose intravenous BP, ONJ appears to be dependent on the dose and duration of therapy, with an estimated incidence of 1%-12% at 36 months of exposure. In osteoporosis patients, it is rare, with an estimated incidence < 1 case per 100,000 person-years of exposure. The incidence of ONJ in the general population is not known. Currently, there is insufficient evidence to confirm a causal link between low-dose BP use in the osteoporosis patient population and ONJ. We concluded BP associated ONJ is associated with high-dose BP therapy primarily in the oncology patient population. Prevention and treatment strategies are currently based on expert opinion and focus on maintaining good oral hygiene and conservative surgical intervention.

Khan AA, Hodsman AB, Papaioannou A, Kendler D, Brown JP, Olszynski WP. · Division of Endocrinology and Geriatrics, Department of Medicine, McMaster University, Hamilton, Ont. · CMAJ. · Pubmed #17261833 links to  free full text

Abstract: In 2002, Osteoporosis Canada published clinical practice guidelines for the diagnosis and management of osteoporosis. The current paper supplements that guideline and provides a review and synthesis of the current literature on the diagnosis and management of osteoporosis in men.

Olszynski WP, Shawn Davison K, Adachi JD, Brown JP, Cummings SR, Hanley DA, Harris SP, Hodsman AB, Kendler D, McClung MR, Miller PD, Yuen CK. · Department of Medicine, University of Saskatchewan, Saskatoon Osteoporosis Centre, Saskatoon, Saskatchewan, Canada. · Clin Ther. · Pubmed #14996514 No free full text.

Abstract: BACKGROUND: Osteoporosis and fragility fractures in men account for substantial health care expenditures and decreased quality of life. OBJECTIVE: This article reviews the most current information about the epidemiology, diagnosis, prevention, and treatment of osteoporosis in men. METHODS: Relevant literature was identified through a search of MEDLINE (1966-June 2003) limited to English-language studies in men. The search terms included fractures, bone density, or osteoporosis plus either epidemiology, diagnosis, prevention, control, or therapy. Additional search terms included specific subtopics (eg, bisphosphonates, calcium, exercise, parathyroid hormone). The authors contributed additional relevant publications. RESULTS: Morbidity after fragility fracture is at least as high in men as in women, and the rate of fracture-related mortality 1 year hip fracture is approximately double in men compared with women. The bioavailable fraction of testosterone slowly declines into the ninth decade in men. There is evidence that the effect of estrogen on bone is greater than that of testosterone in men. Diagnosing osteoporosis in men is complicated by a lack of consensus on how it should be defined. Significant risk factors for osteoporosis or fracture include low bone mineral density, previous fragility fracture, maternal history of fracture, marked hypogonadism, smoking, heavy alcohol intake or alcoholism, low calcium intake, low body mass or body mass index, low physical activity, use of bone-resorbing medication such as glucocorticoids, and the presence of such conditions as hyperthyroidism, hyperparathyroidism, and hypercalciuria. Prevention is paramount and should begin in childhood. During adulthood, calcium (1000-1500 mg/d), vitamin D (400-800 IU/d), and adequate physical activity play crucial preventive roles. When treatment is indicated, the bisphosphonates are the first choice, whereas there is less support for the use of calcitonin or androgen therapy. Parathyroid hormone (1-34) is a promising anabolic therapy. There is also strong evidence for the use of bisphosphonates for the treatment of glucocorticoid-induced osteoporosis.

Kendler D, Kung AW, Fuleihan Gel-H, González González JG, Gaines KA, Verbruggen N, Melton ME. · St. Vincent's Hospital, 120-809 W 41 Avenue, Vancouver, BC, Canada V5Z 2N6. · Maturitas. · Pubmed #15207890 No free full text.

Abstract: OBJECTIVES: Once weekly dosing of alendronate has been shown to provide equivalent efficacy to once daily dosing for treatment of osteoporosis in postmenopausal women. Whether patients will prefer weekly dosing to daily dosing for a chronic condition such as osteoporosis has not been studied. The aim of this international study was to assess preference for the weekly or daily dosing regimen of alendronate among postmenopausal women with osteoporosis. METHODS: This randomised open-label crossover study was conducted at 45 study sites in 19 countries. Four hundred and six postmenopausal women with osteoporosis were assigned randomly to treatment with either alendronate 70 mg once weekly for 4 weeks followed by alendronate 10 mg once daily for 4 weeks or vice versa. The main outcome was the responses of the participants to the Dosing Regimen Questionnaire administered at the end of the study. RESULTS: Of the participants expressing a preference, 84% preferred the once weekly dosing regimen with alendronate to the once daily dosing regimen. In addition, the once weekly regimen was considered by 87% of the participants to be more convenient and was the regimen most of the participants (84%) would be more willing to take for a long period of time (P < 0.001 for each parameter). CONCLUSIONS: The majority of postmenopausal women with osteoporosis preferred the once weekly to the once daily dosing regimen of alendronate. Physicians should consider patient preference for dosing regimen when selecting the appropriate treatment for osteoporosis.

Orwoll E, Ettinger M, Weiss S, Miller P, Kendler D, Graham J, Adami S, Weber K, Lorenc R, Pietschmann P, Vandormael K, Lombardi A. · Oregon Health Sciences University, Portland 97201, USA. · N Engl J Med. · Pubmed #10979796 links to  free full text

Abstract: BACKGROUND: Despite its association with disability, death, and increased medical costs, osteoporosis in men has been relatively neglected as a subject of study. There have been no large, controlled trials of treatment in men. METHODS: In a two-year double-blind trial, we studied the effect of 10 mg of alendronate or placebo, given daily, on bone mineral density in 241 men (age, 31 to 87 years; mean, 63) with osteoporosis. Approximately one third had low serum free testosterone concentrations at base line; the rest had normal concentrations. Men with other secondary causes of osteoporosis were excluded. All the men received calcium and vitamin D supplements. The main outcome measures were the percent changes in lumbar-spine, hip, and total-body bone mineral density. RESULTS: The men who received alendronate had a mean (+/-SE) increase in bone mineral density of 7.1+/-0.3 percent at the lumbar spine, 2.5+/-0.4 percent at the femoral neck, and 2.0+/-0.2 percent for the total body (P<0.001 for all comparisons with base line). In contrast, men who received placebo had an increase in lumbar-spine bone mineral density of 1.8+/-0.5 percent (P<0.001 for the comparison with base line) and no significant changes in femoral-neck or total-body bone mineral density. The increase in bone mineral density in the alendronate group was greater than that in the placebo group at all measurement sites (P<0.001). The incidence of vertebral fractures was lower in the alendronate group than in the placebo group (0.8 percent vs. 7.1 percent, P=0.02). Men in the placebo group had a 2.4-mm decrease in height, as compared with a decrease of 0.6 mm in the alendronate group (P=0.02). Alendronate was generally well tolerated. CONCLUSIONS: In men with osteoporosis, alendronate significantly increases spine, hip, and total-body bone mineral density and helps prevent vertebral fractures and decreases in height.

Reid DM, Hosking D, Kendler D, Brandi ML, Wark JD, Marques-Neto JF, Weryha G, Verbruggen N, Hustad CM, Mahlis EM, Melton ME. · Department of Medicine & Therapeutics, University of Aberdeen, Aberdeen, UK. · Int J Clin Pract. · Pubmed #18324951 No free full text.

Abstract: OBJECTIVES: To compare alendronate 70 mg once weekly (OW) with risedronate 35 mg OW with respect to change in bone mineral density (BMD), biochemical markers and upper gastrointestinal (UGI) tolerability over 24 months. METHODS: This was a 12-month extension to the Fosamax Actonel Comparison Trial international study (FACTS). Postmenopausal women with osteoporosis randomly assigned to either alendronate 70 mg OW or risedronate 35 mg OW for the 12-month base study continued taking the same double-blind study medication. Efficacy measurements were BMD at the hip trochanter, lumbar spine, total hip, and femoral neck and levels of four bone turnover markers at 24 months. The primary hypothesis was that alendronate would produce a greater mean per cent increase from baseline in hip trochanter BMD at 24 months. RESULTS: Trochanter BMD increased significantly from baseline to month 24 in both groups, with a significantly larger increase with alendronate: adjusted mean treatment difference of 1.50% (95% confidence interval: 0.74%, 2.26%; p < 0.001). Similar results were seen at all BMD sites. Significant geometric mean per cent decreases (p < 0.001) from baseline were seen for all four bone turnover markers in both groups, with significantly larger decreases (p < 0.001) with alendronate: adjusted mean treatment differences ranged from 8.9% to 25.3%. No significant differences were seen in incidence of UGI or other adverse events. CONCLUSIONS: Alendronate 70 mg OW yielded significantly greater BMD gains and larger decreases in bone turnover marker levels than risedronate 35 mg OW over 24 months, with no difference in UGI tolerability.

Recker RR, Kendler D, Recknor CP, Rooney TW, Lewiecki EM, Utian WH, Cauley JA, Lorraine J, Qu Y, Kulkarni PM, Gaich CL, Wong M, Plouffe L, Stock JL. · Creighton University, Osteoporosis Research Center, 601 North 30th Street, Suite 5766, Omaha, NE 68131, USA. · Bone. · Pubmed #17182297 No free full text.

Abstract: The double-blind, randomized raloxifene alendronate comparison trial was the first study designed to compare two osteoporosis therapies head-to-head for fracture risk reduction. The original protocol planned to treat 3000 postmenopausal women with alendronate 10 mg/day (ALN) or raloxifene 60 mg/day (RLX) for 5 years, and to recruit women (50-80 years old) with a femoral neck bone mineral density (BMD) T-score between -2.5 and -4.0, inclusive, no prevalent vertebral fractures, and no prior bone-active agent use. The trial was stopped early, due to difficulty in finding treatment-naïve women to meet enrollment goals within the planned timeline, resulting in insufficient power to show non-inferiority between therapies in the primary endpoint (number of women with >or=1 new osteoporotic vertebral or nonvertebral fracture). Except for vertebral fractures, fracture analyses were based upon 1412 of the 1423 women randomized (mean age of 66 years). After 312+/-254 days (mean+/-SD), 22 women in the ALN group and 20 in the RLX group had new vertebral or nonvertebral fractures. Four women in the ALN group and none in the RLX group had moderate/severe vertebral fractures, a pre-specified endpoint (P=0.04). Lumbar spine, femoral neck, and total hip BMD were increased from baseline at 2 years in each group (P<0.001), with greater increases in the ALN group (each P<0.05). Similar numbers of women in each group had >or=1 adverse event and discontinued due to an adverse event. The only adverse events with an incidence that differed between groups were colonoscopy, diarrhea, and nausea; each was more common with ALN treatment (each P<0.05). One woman in each group had a venous thromboembolic event. One case of breast cancer occurred in each group. In summary, as this trial was terminated early, there was insufficient power to compare the fracture risks between alendronate and raloxifene. Safety profiles were as expected from clinical trial and post-marketing reports. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00035971.

Reid DM, Hosking D, Kendler D, Brandi ML, Wark JD, Weryha G, Marques-Neto JF, Gaines KA, Verbruggen N, Melton ME. · Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK. · Clin Drug Investig. · Pubmed #17163237 No free full text.

Abstract: BACKGROUND: The objective of the study was to evaluate the effects of alendronic acid once weekly relative to risedronic acid once weekly on bone mineral density (BMD), markers of bone turnover and tolerability in the treatment of osteoporosis in postmenopausal women. METHODS: This was a randomised, double-masked, double-dummy multicentre international study (75 centres in 27 countries in Europe, the Americas and Asia-Pacific). A total of 1303 women were screened and 936 with low bone density (T-score < or = -2.0 at the spine, hip trochanter, total hip or femoral neck) were randomised; 91% (n = 854) completed the study. Patients were randomised to treatment with either active alendronic acid 70 mg weekly (Fosamax) and placebo identical to risedronic acid weekly or active risedronic acid 35 mg weekly (Actonel) and placebo identical to alendronic acid weekly for 12 months. The primary efficacy endpoint was the percentage change from baseline in hip trochanter BMD at 12 months. Secondary endpoints included the percentage change from baseline in lumbar spine, total hip and femoral neck BMD; biochemical markers of bone turnover (including serum bone-specific alkaline phosphatase [BSAP] and urinary type I collagen N-telopeptides [NTx]); and safety and tolerability as assessed by reporting of adverse experiences. RESULTS: Alendronic acid produced greater increases in BMD than did risedronic acid at 12 months at all sites measured. Mean percentage increases from baseline in hip trochanter BMD at month 12 were 3.56% and 2.71% in the alendronic acid and risedronic acid groups, respectively (treatment difference [95% CI]: 0.83% [0.22, 1.45; p = 0.008]). Mean percentage increases from baseline were greater with alendronic acid than risedronic acid at the lumbar spine, total hip and femoral neck BMD at month 12 (p = 0.002, p < 0.001, p = 0.039, respectively). Increases in BMD with alendronic acid compared with risedronic acid were also significantly greater at 6 months at the trochanter and total hip. There was a greater reduction in bone turnover with alendronic acid compared with risedronic acid: NTx decreased 58% with alendronic acid compared with 47% with risedronic acid at 12 months (p < 0.001); and BSAP decreased 45% with alendronic acid compared with 34% with risedronic acid at 12 months (p < 0.001). Overall tolerability and upper gastrointestinal tolerability were similar for both agents. CONCLUSIONS: Alendronic acid once weekly produced greater BMD increases at both hip and spine sites and greater reductions in bone turnover relative to risedronic acid once weekly. Both agents were well tolerated with no significant difference in upper gastrointestinal adverse experiences. Clinicians should consider these results when making treatment decisions for postmenopausal women with osteoporosis.

Siminoski K, Jiang G, Adachi JD, Hanley DA, Cline G, Ioannidis G, Hodsman A, Josse RG, Kendler D, Olszynski WP, Ste Marie LG, Eastell R. · Department of Radiology and Diagnostic Imaging and Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Alberta, Edmonton, Canada. · Osteoporos Int. · Pubmed #15309381 No free full text.

Abstract: Vertebral fractures are the most common type of osteoporotic fracture, but more than two-thirds remain undetected. We have examined the relationship between height loss and the development of new vertebral fractures to determine whether there is a height loss threshold that has useful clinical accuracy to detect new fractures. We studied 985 postmenopausal women with osteoporosis in the placebo arms of the Vertebral Efficacy with Risedronate Therapy studies. Height was measured annually for 3 years using a wall-mounted stadiometer. New fractures were determined using quantitative and semi-quantitative radiographic morphometry. The relationship between height loss over three years and the number of new vertebral fractures was: height loss (cm) = 0.95 x number of new vertebral fractures-0.4 cm (r = 0.33). The odds ratio for the development of a new fracture increased up to 20.6 (95% confidence interval, 9.3, 45.8) when height loss was greater than 4.0 cm. At a threshold of > 2.0 cm height loss over 3 years, sensitivity was 35.5% for detecting new vertebral fractures and specificity was 93.6%. These findings show that there is a strong relationship between the amount of height loss and the risk of a new vertebral fracture. While there is no cut-off that can reliably rule in a new fracture, height loss of < or = 2.0 cm over 1-3 years has acceptable accuracy for ruling out an incident fracture.

Kendler D. · No affiliation provided · S Afr Med J. · Pubmed #16955946 links to  free full text

This publication has no abstract.