Protocolo clínico de pacientes con historia de uso de bifosfonatos / Clinical protocol for patients with history of use of biphosphonates

Los bifosfonatos son un grupo de medicamentos que se han estadoutilizando en los últimas décadas para el tratamiento de padecimientos que se caracterizan por destrucción o pérdida ósea, cáncer, menopausiay enfermedades óseas no malignas por lo cual es muy importante realizar una amplia y correcta historia clínica para evitar las posibles complicaciones en la fase de cicatrización de los procedimientos quirúrgicos odontológicos. Al atender a un paciente con antecedentes de haber usado este medicamento, se debe conocer la farmacocinética y farmacodinamia para poder planificar el tratamiento pre-, trans- y postoperatorio de los pacientes que serían sometidos principalmente a extracciones dentarias, por lo cual actualmente se puede clasificar a este tipo de pacientes de acuerdo a los resultados de la prueba de laboratorio de la proteína C-telopéptido. Una vez determinado el riesgo del paciente de acuerdo a los resultados de dicha prueba se puede realizar un plan de tratamiento más seguro y eficaz para el paciente en donde se tomen las precauciones necesarias para no evitar una osteonecrosis mandibular o maxilar. Se presenta un caso clínico de un paciente con historia de bifosfonatos en donde se hace el tratamiento de acuerdo a los lineamientos actuales para tratar a este tipo de pacientes.

Bisphosphonates are a group medications that have been used for the last decades for the treatment of conditions that are characterized bybone loss or destruction, cancer, menopause and non-malignant bone diseases, which is why it is very important to make a broad and correctmedical history to avoid the possible complications in the healing phaseof dental surgical treatments. When treating a patient with a history of this drug we should know the pharmacokinetics and pharmacodynamics to be able to plan the pre, trans and postoperative treatment of patientsmainly subject to dental extractions, which is why currently this type ofpatients can be classified according to the results of the laboratory testof the C-Telopeptide protein. Once the patient’s risk has been determined according to the results of this test, an effective and safe treatmentplan can be started for the patient in which the necessary precautionsare taken to not develop a mandibular or maxillary osteonecrosis. We present a case of a patient with a history of bisphosphonates wherethe treatment is done according to the current guidelines for treatingthis type of patients.

Review on the comparison of effectiveness between denosumab and bisphosphonates in post-menopausal osteoporosis

OBJECTIVE: Osteoporosis is a rapidly rising cause of concern for elderly patients. Various classes of drugs are available in the market. Bisphosphonates are considered as a first-line therapy for the prevention and treatment. Denosumab is an antiresorptive agent which is a RANK ligand inhibitor. There is a scarcity of comparison between these two classes of drugs. The aim of this study is to compare efficacy of Bisphosphonates and Denosumab in various parameters. MATERIALS AND METHODS: Literature search was done for randomized controlled trials (RCTs) comparing bisphosphonates with denosumab. RCTs with a treatment period of at least one year with a baseline bone mineral density (BMD) and bone turnover markers (BTM) and follow up values at one year were included in the study. All included studies were also analysed for complications. The study has also been registered in PROSPERO International prospective register of systematic reviews. RESULTS: A total of five RCTs were identified providing data on 3751 participants. In all five studies, the BMD changes at both hip and spine were statistically significant in favour of denosumab. Result was similar in three studies that studied BMD changes at the wrist. Denosumab also produced significant reduction in BTM as early as one month, but at one year there was no difference compared to the bisphosphonates. There was no statistically significant differences in the complication rates. CONCLUSION: Though both bisphosphonates and denosumab were effective with similar side effects, the latter was statistically superior in increasing the BMD and reducing the BTM.

Effects of close-to-bone needling on expression of type-Ⅱ collagen and markers in cartilage in rabbits with osteoarthritis of knee and imaging observation / 中国针灸

<p><b>OBJECTIVE</b>To observe the effects of close-to-bone needling (CBN) on the expressions of type-Ⅱcollagen, pro-collagen type Ⅱ C-terminal propeptide (PⅡCP) and C-telopeptide of type Ⅱ collagen (CTX-Ⅱ) in rabbits with knee osteoarthritis (KOA).</p><p><b>METHODS</b>Among 40 New Zealand rabbits, 10 rabbits were selected into a normal group; the remaining 30 rabbits were made into KOA model, and X-ray was used to evaluate the results of model establishment. After the model was successfully made, the rabbits were randomly divided into a model group, a CBN group and a regular acupuncture group, ten rabbits in each one.Rabbits in the CBN group and the regular acupuncture group were treated at "Neixiyan" (EX-LE 4), "Dubi" (ST 35), "Yinlingquan" (SP 9), "Zusanli" (ST 36) and "Liangqiu" (ST 34). The CBN group applied CBN, and the depth of needling was appropriate with needles reaching bone; the regular acupuncture group applied regular acupuncture. The electroacupuncture(EA) device was used in the two groups, 20 min per treatment, once a day.Five days of treatment were taken as one course, and totally 4 courses were given with an interval of 2 days between courses. The normal group received identical fixation as model group. After treatment, magnetic resonance imaging (MRI) was used to perform imaging observation on knee; transmission electron microscopy (TEM) was used to observe the cell structure of knee joint cartilage;HE staining was used to observe the pathological change of knee; TUNEL was used to observe the apoptotic index; the expressions of type-Ⅱ collagen proteins and mRNA were measured by Western-blot and reverse transcription-polymerase chain reaction (RT-PCR); the serum PⅡCP and CTX-Ⅱ levels were measured using enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>After treatment, compared with the model group, in the CBN group and regular acupuncture group the articular cavity effusion was reduced without the subchondral bone edema; the cell structure of knee joint cartilage was regular with less apoptosis; the expressions of type-Ⅱ collagen proteins and mRNA were significantly increased (all<0.05), the PⅡCP levels were significantly increased (both<0.05), but the CTX-Ⅱ levels were significantly decreased (both<0.05).The differences of the expressions of type-Ⅱ collagen proteins and mRNA, the levels of PⅡCP and CTX-Ⅱ between the CBN group and the regular acupuncture group were significant (all<0.05); the differences between the CBN group and the normal group were non-significant (all>0.05).</p><p><b>CONCLUSIONS</b>CBN can significantly improve the pathological status of cartilage of KOA, reduce apoptosis, and is likely to regulate the expressions of PⅡCP and CTX-Ⅱ to promote the type-Ⅱ collagen, which is superior to regular acupuncture.</p>

Effect of Combined Sex Hormone Replacement on Bone/Cartilage Turnover in a Murine Model of Osteoarthritis

BACKGROUND: Estrogens act on estrogen receptors distributed in articular cartilages, synovial membrane, and ligaments, which are thought to be related with degenerative changes. Meanwhile, progesterone is known to have a weak anabolic action on bone formation This study evaluates the effects of estrogen and progesterone hormone on bone/cartilage turnover in ovariectomized (OVX) rats. METHODS: Thirty-five 7-month-old female Sprague-Dawley rats were randomly divided into 5 groups and then ovariectomized bilaterally except the sham control group. The first and the second group acting as controls did not receive hormonal therapy, the third group received estrogen, the fourth group received progesterone, and the fifth group received combination of both hormones 10 weeks after surgery. Evaluations were done using the serum levels of cartilage oligomeric matrix protein (COMP) for cartilage turnover, collagen type I C-telopeptide (CTX-1) and osteocalcin (OC) for bone turnover at 11, 15, 19 weeks after OVX and histology using the Osteoarthritis Research Society International (OARSI) osteoarthritis (OA) cartilage histopathology assessment system. RESULTS: Significantly less cartilage degradation (decreased levels of COMP) was found in the combined hormone treated group in comparison with OVX group. Similarly, both hormonal treatment resulted in increased bone formation and decreased bone resorption i.e., a low overall bone turnover status (decrease in the serum OC and CTX-1 levels). CONCLUSIONS: Combined estrogen and progesterone therapy was found to be convincing in terms of reducing the severity of OA in this experimental model.

The Association between Bone Mineral Density, Bone Turnover Markers, and Nutrient Intake in Pre- and Postmenopausal Women

The purpose of this study was to examine the association among bone mineral density (BMD), biochemical bone markers, nutrients, and salt intake in premenopausal and postmenopausal women. We evaluated 431 subjects who visited a health promotion center of a university hospital between January 2008 and July 2009. We excluded those who were taking medications or who had an endocrine disorder affecting osteoporosis. The subjects were divided into premenopausal (n = 283) and postmenopausal (n = 143) women. We evaluated the correlation among BMD of the lumbar spine, femoral neck, and total femoral, as well as biochemical bone markers, hormone, serum profiles, general characteristics, nutrient intakes, and food intake frequencies. From a stepwise multiple regression analysis, lumbar spine BMD was positively correlated with weight (p < 0.001) and negatively correlated with osteocalcin (OC)(p < 0.001), Femoral neck BMD was positively correlated with weight (p < 0.001) and negatively correlated with C-telopeptide (CTx) and alkaline phosphatase (ALP)(p < 0.001, p < 0.05). In premenopausal women, femoral total BMD was positively correlated with BMI (p < 0.001) and negatively correlated with CTx (p < 0.001). In postmenopausal women, lumbar spine BMD was positively correlated with calcium intake (p < 0.01) and negatively correlated with sodium intake (p < 0.01). Femoral neck and femoral total BMD were both positively correlated with weight (p < 0.001), and femoral neck BMD was negatively correlated with age and ALP (p < 0.001, p < 0.05). Femoral total BMD was negatively correlated with age and OC (p < 0.001, p < 0.01). These results suggest that reducing sodium intake may play an important role delaying bone resorption and preventing a decrease in BMD.

The significance of serum C-telopeptide as a bone marker in chronic hemodialysis patients / 대한내과학회지

BACKGROUND/AIMS: Checking bone mineral density (BMD) is not sufficient for determining the progression of renal osteodystrophy. Measuring pyridinoline or deoxypyridinoline in urine does not give an accurate bone status, due to insufficient urine in patients with renal failure. However, another biochemical marker, beta-CTX (the carboxy-terminal telopeptide of type 1 collagen), in serum is believed to be a good indicator of the status of renal osteodystrophy. METHODS: Fifty-nine patients undergoing hemodialysis agreed to have their blood and BMD checked. Beta-CTX was measured using an electro-chemiluminescence sandwich immunoassay and BMD was counted at the lumbar spine, femoral neck, and distal humerus using a Discovery-Wi (Hologic). RESULTS: Bone-alkaline phosphatase (49.8+/-36.7 U/L), parathormone (PTH) (192.8+/-263.3 U/L), osteocalcin (33.4+/-18.2 ng/mL), and beta-CTX (2.1+/-1.2 ng/mL) were all increased, while the average BMD of the lumbar spine (0.86+/-0.17), femoral neck, (0.67+/-0.14) and distal humerus (0.67 +/- 0.17) were all decreased. The BMD of the femoral neck in females was significantly lower than in males (p=0.044). The serum phosphate and PTH concentrations in non-diabetics were significantly higher than in diabetics (p=0.001, p=0.04, respectively). The measured serum osteocalcin and beta-CTX concentrations in patients older than 40 years were much lower than in patients younger than 40 (p=0.009, p=0.01, respectively). Beta-CTX was strongly correlated with bone-alkaline phosphatase (r=0.625, p=0.00), osteocalcin (r=0.698, p=0.00), and PTH (r=0.648, p=0.00). CONCLUSIONS: Beta-CTX is another convenient, significant marker for evaluating renal osteodystrophy.

Age and Sex Specific Reference Ranges of Serum Type I Collagen C-telopeptide and Osteocalcin Based on Menstrual Stage / 임상검사와정도관리

BACKGROUND: Bone turnover markers (BTMs) are widely used tool for monitoring the response to osteoporosis therapy, and the normal adult reference range is the baseline value for the treatment of osteoporosis with anti-resorptive agents. This study was aimed to establish age- and sex-specific reference ranges of serum osteocalcin and serum type I collagen C-telopeptide (S-CTX) in adults based on menstrual stage. METHODS: Serum osteocalcin, S-CTX and bone mineral density (BMD) were measured in 291 adults (men: 162, women: 129), and follicle stimulating hormone (FSH) in women. Seven women whose serum FSH levels were >30 IU/mL were categorized as perimenopausal despite their regular menses. RESULTS: Among females with normal BMD, there were no difference in serum osteocalcin and S-CTX levels between premenopausal and postmenopausal women. Females with osteopenia in pre- and postmenopausal stage showed higher serum osteocalcin and S-CTX levels than females with normal BMD. For subjects with normal BMD, reference ranges of serum osteocalcin and S-CTX were 6.4~21.6 ng/mL and 0.08~0.85 ng/mL for 30~59-year-old females. For males with normal BMD, reference ranges of serum osteocalcin were 10.1~24.3 ng/mL for 30~39 years old and 7.7~22.4 ng/mL for 40~59 years old, and reference range of CTX was 0.13~1.27 ng/mL for 30~59 years old. CONCLUSIONS: This study will provide a redefinition of the criteria required in order to establish the normal reference ranges for BTMs. Moreover, we believe that our data will come in handy when used as normal reference ranges of BTMs in premenopausal women.

Hip joint fracture and bone metabolic biochemical index of the aged patients / 中国矫形外科杂志

[Objective] To study the bone metabolic biochemical index of the aged patients with hip fracture,for better predicting the future risk of the old people' s hip fracture.[Method]50 cases of sufferers(over 60 years old) with hip fracture(28 males,and 22 females) and 30 cases of healthy aged people(15 males,and 15 females) were selected to analyze Ⅰ Collagen crosslinked c-telopeptide(ICTP),deoxypyridino line(Dpd) in urine,and serum bone glaprotein(BGP).[Result](1)The mean level of ICTP and Dpd in urine in aged hip fracture group was higherthan that of the control group(P0.05).[Conclusion]Bone absorbability in the aged hip fracture patients is higher than in the aged healthy people.The analysis of ICTP and Dpd in urine may /might give some reference value in preventing and treatlng aged hip fracture patients.

Evaluation of Serum CTX and Osteocalcin Using Elecsys 2010 / 대한임상병리학회지

BACKGROUND: In contrast with bone formation markers, most of available indices of bone resorption are urine markers and show relatively high degree of variability. The serum resorption assay has therefore been developed. We evaluated serum bone-derived degradation products of type I collagen C-telopeptide (s-CTX) and serum osteocalcin by Elecsys 2010 (Hitachi Boehringer Mannheim, Tokyo, Japan). METHODS: For 18 healthy controls, 15 osteopenic and 7 osteoporotic patients samples, serum CTX and serum osteocalcin were measured by Elecsys 2010 using -CrossLaps/serum (Roche Diagnostic Corp., Indianapolis, USA) kit and N-MID Osteocalcin (Roche Diagnostic Corp. kit, respectively. DPD by Immulite (Diagnostic Products Corp., LA, USA) using Pyrilinks-D(TM) (Diagnostic Products Corp.) kit and serum osteocalcin for correlation by Gamma counter (Hewlett Packard, Meriden, USA) using ELSA-OSTEO (CIS, Cedex, France) kit were measured. RESULTS: The within-run and between-run coefficient of variation (CV) values of s-CTX were 6.41% and 6% in low concentrations and 3.84% and 7% in high concentrations, respectively. The within-run and between-run CV values of serum osteocalcin were 2.21% and 6% in low concentrations and 1.25% and 3% in high concentrations, respectively. The dilution recovery of s-CTX and serum osteocalcin was 100-169% (mean, 134%) and 80-138% (mean, 104%), respectively. S-CTX and DPD (R=0.369, P=0.019), and serum osteocalcin by Elecsys 2010 and RIA (R=0.889, P<0.001) showed positive correlations, respectively. CONCLUSTIONS: S-CTX and serum osteocalcin by Elecsys 2010 exhibits good analytical performance and correlate with DPD and serum osteocalcin by RIA, respectively. Therefore, these may replace DPD and serum osteocalcin by RIA and can be used for bone resorption and formation markers, respectively.