Claude A Kraenzlin

Loma Linda University, Loma Linda, California, United States

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Publications (10)33.42 Total impact

  • C Meier · C Kraenzlin · N F Friederich · T Wischer · L Grize · C R Meier · M E Kraenzlin ·
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    ABSTRACT: Based on this double-blind, placebo-controlled study, ibandronate has no beneficial effect on clinical and radiological outcome in patients with spontaneous osteonecrosis of the knee over and above anti-inflammatory medication. Observational studies suggest beneficial effects of bisphosphonates in spontaneous osteonecrosis (ON) of the knee. We investigated whether ibandronate would improve clinical and radiological outcome in newly diagnosed ON. In this randomized, double-blind, placebo-controlled trial, 30 patients (mean age, 57.3 ± 10.7 years) with ON of the knee were assigned to receive either ibandronate (cumulative dose, 13.5 mg) or placebo intravenously (divided into five doses 12 weeks). All subjects received additional treatment with oral diclofenac (70 mg) and supplementation with calcium carbonate (500 mg) and vitamin D (400 IU) to be taken daily for 12 weeks. Patients were followed for 48 weeks. The primary outcome was the change in pain score after 12 weeks. Secondary endpoints included changes in pain score, mobility, and radiological outcome (MRI) after 48 weeks. At baseline, both treatment groups (IBN, n = 14; placebo, n = 16) were comparable in relation to pain score and radiological grading (bone marrow edema, ON). After 12 weeks, mean pain score was reduced in both ibandronate- (mean change, -2.98; 95 % CI, -4.34 to -1.62) and placebo- (-3.59; 95 % CI, -5.07 to -2.12) treated subjects (between-group comparison adjusted for age, sex, and osteonecrosis type, p = ns). Except for significant decrease in bone resorption marker (CTX) in ibandronate-treated subjects (p < 0.01), adjusted mean changes in all functional and radiological outcome measures were comparable between treatment groups after 24 and 48 weeks. In patients with spontaneous osteonecrosis of the knee, bisphosphonate treatment (i.e., IV ibandronate) has no beneficial effect over and above anti-inflammatory medication.
    Osteoporosis International 11/2013; 25(1). DOI:10.1007/s00198-013-2581-5 · 4.17 Impact Factor
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    ABSTRACT: Background: Intravenous bisphosphonates are widely used for treatment of postmenopausal osteoporosis. They are associated with transient influenza-like symptoms, predominantly after the first zoledronic acid (up to 32 %) or ibandronate (up to 5 %) administration. The experience in clinical practice suggests that the incidence of post-dose symptoms is higher than has been reported in clinical trials. We assessed the safety of annual infusions of zoledronic acid and 3-monthly injections of ibandronate in women with postmenopausal osteoporosis. Methods: In this retrospective study we analysed safety data from 272 postmenopausal women treated with zoledronic acid (n = 127; mean age 68.6 ± 9.4 years) or intravenous (IV) ibandronate (n = 145; mean age 69.1 ± 9.0 years). Safety data (including occurrence of acute-phase reactions and osteonecrosis of the jaw) were gathered in phone call interviews by using a standardized questionnaire. Results: The number of patients with adverse events was significantly higher in zoledronic acid as compared to ibandronate-treated patients, primarily because of a larger number of post-dose symptoms after bisphosphonate administrations (54.3 % vs. 33.1 %, p < 0.001). Except for occurrence of fever (more common after zoledronic acid infusion), other influenza-like symptoms (myalgia, arthralgia, headache) appeared in a similar proportion of patients after IV treatment (within 24-36 h). Symptoms lasted for >3 days in approximately 50 % of patients. The incidence of symptoms decreased after subsequent infusions. The rate of influenza-like symptoms was more frequent after zoledronic acid than after IV ibandronate in bisphosphonate-naïve patients but comparable in patients pretreated with oral bisphosphonates. There were no spontaneous reports of osteonecrosis of the jaw, arrhythmia or delayed fracture healing. Conclusion: Although IV bisphosphonates are generally safe, the occurrence of transient influenza-like symptoms after IV bisphosphonates seems to be more frequent in clinical practice than has been reported in clinical trials.
    Clinical Drug Investigation 11/2012; 33(2). DOI:10.1007/s40261-012-0041-1 · 1.56 Impact Factor
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    ABSTRACT: Osteonecrosis (ON) in the knee occurs as a localized inflammatory disease in relation to spontaneous or non-traumatic ON. Conservative treatment possibilities are limited, and prognosis appears to be poor; in most cases, ON results in knee arthroplasty. Bisphosphonates are suggested to prevent bone resorption and collapse of necrotic bone. In this observational, prospective study we investigated the effect of bisphosphonate treatment in patients with spontaneous or arthroscopy-induced ON of the knee. Twenty-eight patients with osteonecrotic lesions and bone marrow oedema in the knee were included. In 22 patients (80%), ON was identified after arthroscopic surgery of the knee; six patients were diagnosed with spontaneous ON. Patients were initially given pamidronate 120 mg i.v. divided in 3-4 perfusions over 2 weeks, followed by oral bisphosphonate treatment with alendronate 70 mg weekly for 4-6 months. Bisphosphonate treatment resulted in a rapid pain relief, VAS decreasing from 8.2 ± 1.2 at baseline to 5.02 ± 0.6 after 4-6 weeks (p < 0.001). After 6 months, the VAS decreased by 80% (p < 0.001). At the 6-month follow-up, symptoms had resolved completely in 15 patients out of 28; in 6 patients, minimal symptoms (VAS 1-2) remained. In two patients, treatment effect was unsatisfactory, and surgical intervention was needed (arthroplasty). Bone marrow oedema on MRI resolved completely in 18 patients out of 28 with substantial reduction in the remaining. Furthermore, osteonecrotic area resolved completely or demarcation with sclerotic changes of the necrotic area could be observed. Bisphosphonate treatment in patients with osteonecrosis of the knee was associated with a rapid improvement in pain score and radiological consolidation of the area of osteonecrosis. Further randomized, controlled trials are warranted to confirm the potential beneficial role of bisphosphonates in the treatment of osteonecrosis of the knee. Level of evidence: observational study, level IV.
    Knee Surgery Sports Traumatology Arthroscopy 04/2010; 18(12):1638-44. DOI:10.1007/s00167-010-1106-4 · 3.05 Impact Factor
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    ABSTRACT: In this study, the relationship between fluoride pharmacokinetics and the response in spinal bone density to fluoride treatment was studied in 14 patients with primary osteoporosis treated with fluoride for at least 1 year. Serum concentrations and urinary excretion of fluoride were determined after ingestion of 10 mg fluoride as monofluorophosphate. The pharmacokinetic parameters were calculated according to a linear one-compartment open model. The fasting serum fluoride level was 8.8 +/- 0.98 mumol/liter. The peak serum fluoride level was 20.5 +/- 1.4 mumol/liter and was reached within 2 h after ingestion of fluoride. When the patients were divided into good and poor responders, based on whether they did or did not exhibit a change in spinal bone density of 13 mg/cc per year or more, we found that good responders had decreased renal fluoride clearance (-62 +/- 13%, p less than .02), increased maximum change in serum fluoride (+38 +/- 18%, p less than .01), increased extrarenal clearance (+62 +/- 57%, p less than .05) and increased change in serum alkaline phosphatase (ALP) (+241 +/- 169%, p less than 0.02) compared with poor responders. Our data suggest that one factor accounting for a good response is a relatively high serum level of fluoride. However, although the maximum change in serum fluoride was greater in good responders compared with poor responders, variations in fluoride levels could not explain all of the variation in spinal bone density. Therefore, we propose that in addition to differences in serum fluoride, other factors are also responsible for the good response.
    Journal of Bone and Mineral Research 03/2010; 5 Suppl 1(S1):S49-52. DOI:10.1002/jbmr.5650051370 · 6.83 Impact Factor
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    ABSTRACT: Concurrent use of bisphosphonate therapy reduces the anabolic effect of teriparatide. Consequently, in clinical practice bisphosphonates are discontinued and teriparatide therapy held for a few months to allow bone turnover to increase. We aimed to evaluate the effect of prior bisphosphonate exposure and the effect of bisphosphonate wash-out on the treatment response to teriparatide. Thirty-nine patients with primary osteoporosis (mean age 63.6 +/- 14.0 years), including 26 patients previously treated with oral bisphosphonates (median duration 53 months) and 13 bisphosphonate-naïve patients were started on teriparatide (20 mug daily) and followed prospectively over 12 months. The primary study outcome was change in bone formation markers (PINP, bone ALP, osteocalcin). Secondary outcomes included changes in bone resorption (betaCTX) and 12-month changes in BMD. Markers of bone formation increased early during teriparatide therapy and were followed by an increase in betaCTX (p < 0.001). The magnitude of the increase in bone markers was comparable in both patient groups irrespective of prior bisphosphonate exposure; similarly, increases in BMD after 12 months were not significantly different between bisphosphonate-pretreated and bisphosphonate-naïve patients (lumbar spine 7.1 vs. 8.9%, p = 0.58; total hip 4.1 vs. 1.1%, p = 0.48). The response of teriparatide was not related to the duration of bisphosphonate wash-out (median duration 4.2 months). This study confirms that beneficial effects of teriparatide on intermediate bone endpoints can be translated into clinical practice with less constringent methodological circumstances than in RCTs. Furthermore, as bisphosphonate wash-out does not appear to influence the treatment effect, teriparatide therapy can be started immediately after ceasing bisphosphonate therapy and wash-out.
    Journal of Bone and Mineral Metabolism 06/2009; 28(1):68-76. DOI:10.1007/s00774-009-0101-7 · 2.46 Impact Factor
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    ABSTRACT: The pyridinium cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are established markers of bone resorption. We evaluated the analytical and clinical performance of a commercially available PYD HPLC assay and established reference intervals in children and adults. We used a commercially available reagent set (Chromsystems Instruments & Chemicals) to measure PYD and DPD in 319 healthy controls (156 premenopausal women, 80 healthy men, and 83 healthy children age 1 month to 14 years) and 397 patients with metabolic bone diseases (postmenopausal osteoporosis, n = 175; male osteoporosis, n = 176; hyperparathyroidism, n = 17; hyperthyroidism, n = 19; Paget disease, n = 10). The mean intraassay and interassay CVs were <6% and <8% for both PYD and DPD, respectively. The reference interval was constant for premenopausal women in the age group 20-49 years. In men, cross-link values peaked at 20-29 years and decreased thereafter. Women with postmenopausal osteoporosis had significantly higher PYD (51%) and DPD (58%) values compared to premenopausal women. Similar results were found in osteoporotic men. In children the highest values were found in the first weeks and months after birth, followed by a decrease of 50%-60% at age 11-14 years. In metabolic bone diseases cross-link concentrations were significantly increased. The DPD:PYD ratio (mean value approximately 0.2) was remarkably constant in all populations evaluated. The automated HPLC assay is a precise and convenient method for PYD and DPD measurement. We established reference intervals for adult women and men and for children up to 14 years old. The cross-link concentrations we determined by use of this HPLC method confirm its clinical value in enabling identification of increased bone resorption in patients with metabolic bone diseases.
    Clinical Chemistry 09/2008; 54(9):1546-53. DOI:10.1373/clinchem.2008.105262 · 7.91 Impact Factor
  • M E Kraenzlin · M J Seibel · U Trechsel · V Boerlin · M Azria · C A Kraenzlin · H G Haas ·
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    ABSTRACT: Although treatment with intranasal salmon calcitonin (sCT) has been shown to effectively inhibit postmenopausal bone loss, there is still controversy over both timing and the duration of its application. In an open prospective study, we therefore assessed the effect of shortterm intranasal sCT on postmenopausal bone turnover, employing biochemical markers of bone metabolism. Ten early postmenopausal, previously untreated women (1-5 years after menopause) with biochemical evidence of increased bone resorption and a low bone mineral density at baseline were treated with intranasal sCT (100 IU B.I.D.) for a period of 3 months. Oral calcium (500 mg/day) was administered simultaneously, and during a further 3 month follow-up interval. Treatment with sCT resulted in a pronounced suppression of bone resorption markers with a maximum effect reached after 8 weeks of therapy: as compared to the respective baseline values, mean levels decreased by -26.2% +/- 3.4% (P < 0.001) for pyridinoline, -32.7% +/- 3.5% (P < 0.001) for deoxypyridinoline, -32.7% +/- 3.3% (P < 0.001) for hydroxyproline, and -24.1% +/- 8.2% (P < 0.001) for the amino-terminal telopeptide. In contrast, changes in bone formation markers of osteocalcin (-14.4% +/- 4.8%, P < 0.05) and C-terminal procollagen type I propetide (-7.9% +/- 3.9%, ns) were much less pronounced. Unexpectedly, after week 8 of the study all resorption markers showed a plateau and a trend to increase, although intranasal sCT was continued for a total of 12 weeks. This effect could not be attributed to the formation of anti-sCT antibodies. After cessation of treatment, both bone formation and resorption markers rapidly returned to baseline levels. Bone mineral density of both spine and hip showed no significant change during the observation period. Our results demonstrate that in postmenopausal women with a high bone turnover, intranasal treatment with 200 IU of sCT effectively reduces bone turnover and maintains bone mass, the maximum effect being reached after 8 weeks of treatment.
    Calcified Tissue International 05/1996; 58(4):216-20. DOI:10.1007/BF02508638 · 3.27 Impact Factor
  • M. E. Kraenzlin · C. A. Kraenzlin · H. G. Haas ·
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    ABSTRACT: Without Abstract
    Osteoporosis International 01/1996; 6(S1):246-246. DOI:10.1007/BF02500522 · 4.17 Impact Factor
  • M.E. Kraenzlin · C.A. Kraenzlin · H.G. Haas ·

    Bone and Mineral 04/1992; 17:206. DOI:10.1016/0169-6009(92)92161-I
  • M. Kraenzlin · C. Kraenzlin · H. Haas ·