Bisphosphonates in pregnancy and lactation-associated osteoporosis

Introduction Pregnancy and lactation-associated osteoporosis (PLO) is an uncommon condition characterized by the occurrence of fracture(s) during late pregnancy or the puerperium. The aetiology is uncertain, and its management and natural history poorly defined. Methods We report a series of 11 women with PLO seen at our institution over the past 20 years, with follow-up ranging from 1 to 19 years. Results Ten women presented with painful low-trauma vertebral fractures, at a median of 1 month postpartum. In nine cases the fractures were multiple (median: 3, range: 2–5). At least one recognised risk factor for osteoporosis (low body weight, smoking history, family history of osteoporosis/fracture, vitamin D insufficiency) was present in nine patients. Bone density was in the osteoporotic range at the spine (mean T score: −2.8), with less marked reduction at the proximal femur (mean T score: −1.9). Nine patients received bisphosphonate treatment, for a median duration of 24 months. In the five women who received a bisphosphonate within 1 year of presentation, spinal bone density increased by 23% over baseline values after 2 years of treatment (p=0.0014). Of the 5 women who had subsequent pregnancies, one, who had declined bisphosphonate therapy after the initial presentation, sustained a fracture in the postpartum period. Two patients (both of whom were followed for at least 10 years) sustained fractures outside of pregnancy. Conclusions PLO is therefore associated with significant morbidity, a high prevalence of recognized risk factors for osteoporosis and a risk of recurrence in subsequent pregnancies. Bisphosphonate therapy administered soon after presentation substantially increases spinal bone density in patients with PLO.     

Pharmacogenomics-Potential applications to orthopedic practice

Pharmacogenomics is developing at a rapid pace. Though ethical and financial considerations still exist, physicians should familiarize themselves with this evolving science.     

Hydroxyapatite-coated titanium for orthopedic implant applications

The interface mechanical characteristics and histology of commercially pure (CP) titanium- and hydroxyapatite- (HA) coated Ti-6Al-4V alloy were investigated. Interface shear strength was determined using a transcortical push-out model in dogs after periods of three, five, six, ten, and 32 weeks. Undecalcified histologic techniques with implants in situ were used to interpret differences in mechanical response. The HA-coated titanium alloy implants developed five to seven times the mean interface strength of the uncoated, beadblasted CP titanium implants. The mean values for interface shear strength increased up to 7.27 megaPascals (MPa) for the HA-coated implants after ten weeks of implantation, and the maximum mean value of interface shear strength for the uncoated CP titanium implants was 1.54 MPa. For both implant types there was a slight decrease in mean shear strength from the maximum value to that obtained after the longest implantation period (32 weeks). Histologic evaluations in all cases revealed mineralization of interface bone directly onto the HA-coated implant surface, with no fibrous tissue layer interposed between the bone and HA visible at the light microscopic level. The uncoated titanium implants had projections of bone to the implant surface with apparent direct bone-implant apposition observed in some locations. Measurements of the HA coating material made from histologic sections showed no evidence of significant HA resorption in vivo after periods of up to 32 weeks.     

Roentgen stereophotogrammetry. Review of orthopedic applications

Roentgen stereophotogrammetry is based on radiographic examinations of calibration cages and object markers implanted in the skeleton. Accurate measurements of radiographs and computer-assisted calculations can provide a three-dimensional motion analysis. Since its introduction 15 years ago, roentgen stereophotogrammetry has found an increasing number of orthopedic applications, which are reviewed here: growth, prosthetic fixation, joint kinematics and stability, fracture stability, and the healing course of spinal fusion and pelvic and tibial osteotomies.     

Nanotechnology: the scope and potential applications in orthopedic surgery

Nanotechnology involves manipulation of matter measuring 1–100 nm in at least one of its dimensions at the molecular level. Engineering and manipulation of matter at the molecular level has several advantages in the field of medicine (nanomedicine) since most of the biological molecules exist and function at a nanoscale. Though promising, questions still remain on how much of this will ultimately translate into achieving better patient care. Concerns of cost-effectiveness and nanotechnology safety still remain unclear. Orthopedics is an attractive area for the application of nanotechnology since the bone, and its constituents such as hydroxyapatite, Haversian systems, and the collagen fibrils are nanocompounds. The major orthopedic applications of nanotechnology involve around (i) effective drug delivery systems for antibiotics and chemotherapeutic agents, (ii) surface preparation of implants and prosthesis to improve osteointegration and reduce biofilm formation, (iii) controlled drug eluting systems to combat implant-related infections, (iv) tissue engineering for scaffolds preparation to deal with bone and cartilage defects, and (v) diagnostic applications in the field of oncology and musculoskeletal infections.     

Bisphosphonates in oncology

Bone metastases result in considerable morbidity, often affecting quality of life and independence over years, and may place complex demands on health care resources. The bisphosphonates have been shown to reduce skeletal morbidity in multiple myeloma and solid tumours affecting bone by 30-50%. Quite appropriately, these agents are increasingly used alongside anticancer treatments to prevent skeletal complications and relieve bone pain. The use of bisphosphonates in early cancer has become increasingly important to prevent adverse effects of cancer treatments on bone health. These include chemotherapy induced ovarian failure and the use of aromatase inhibitors in breast cancer and androgen deprivation therapy in prostate cancer. Bisphosphonate strategies, similar to those used to treat post-menopausal osteoporosis, are the intervention of choice for patients with low bone mineral density or rapid bone loss, along with adequate calcium and vitamin D intake and a healthy lifestyle. There is a strong preclinical rationale for bisphosphonates to prevent metastasis, primarily through inhibition of the vicious cycle of metastasis within the microenvironment. Recent data suggest that adjuvant bisphosphonates, at least in some patient subgroups, may modify the course of the disease and disrupt the metastatic process, reducing the risks of disease recurrence. In comparison to most other cancer treatments, adverse events related to bisphosphonate therapy are generally mild and infrequent; thus, the benefits of treatment within licensed indications will almost always outweigh the risks.     

Bisphosphonates in renal osteodystrophy

The present review considers the role that bisphosphonates might have in patients with renal failure. Although bisphosphonates are widely used to reduce fracture risk in patients with osteoporosis, few studies have documented their effect in patients with renal osteodystrophy. The pathogenesis of bone loss after renal transplantation and the role of the recently identified osteoprotegerin/receptor activating nuclear factor-kappaB system is described. Inhibition of bone resorption may prove beneficial when high bone turnover is present, but there are potential drawbacks to widespread use of bisphosphonates. These issues are discussed, with emphasis placed on reports published within the past 18 months.     

Bisphosphonates in orthopaedic surgery

Bisphosphonates are the most clinically important class of antiresorptive agents available to treat diseases characterized by osteoclast-mediated bone resorption. Currently, seven bisphosphonates have the approval of the United States Food and Drug Administration. The most common adult diseases treated with bisphosphonates include osteoporosis, Paget disease, and metastatic bone disease. The treatment of pediatric disorders such as osteogenesis imperfecta and fibrous dysplasia with bisphosphonates has gained momentum, and initial investigations have demonstrated an acceptable safety profile. Currently, there is a lack of long-term follow-up data, which will be necessary for the development of responsible guidelines for therapy.     

骨科手术中异体输血相关因素分析及其临床应用

目的研究骨科手术中异体输血的相关因素,分析其临床意义.方法选择骨科手术457例,用血型群体遗传学等方法,调查输注ABO成分血血型表现型等相关因素及临床意义.结果(1)股骨骨折、腰椎间盘突出症(Lumbar Disc Herniation,LDH)、脊柱侧弯等为主要骨科手术输血适应证,每例总输血量平均为(5.06±2.88)U.(2)患者输血量与性别无相关性,同性别不同适应证及不同性别同种适应证骨科手术输血量无显著差异.(3)患者组与对照组比较,B型表现型频率显著高于对照组(P<0.05),而AB型表现型频率显著低于对照组(P<0.05).结论制定主要骨科手术输血基数,增加一定比例B型且减少一定比例AB型成分血储备,这样可合理预约输血,保证手术中充分有效利用血源.     

镍钛记忆合金骨科器械的基础研究及在手外科应用进展

1963年Buehler报告镍钛合金具有良好的形状记忆效应后,在医学界倍受关注。20世纪70年代以来,国内外对镍钛记忆合金(Nitinol)的基础和临床应用做了大量研究,取得了重大进展。从生物力学的观点分析,骨质的生长和吸收与应力有关,不同部位骨折的愈合对应力/应变的要求不一样,国内许多学者采用不同方法对其研制的Nitinol骨科器械进行了生物力学测试。我国Nitinol器械在手外科的应用始于20世纪80年代,实践表明,疗效满意。本文综述了Nitinol骨科器械的基础研究及在手外科的临床应用进展。     

Bisphosphonates in preclinical bone oncology

Bisphosphonates, especially nitrogen-containing bisphosphonates, are widely used to block bone destruction in cancer patients with bone metastasis because they are effective inhibitors of osteoclast-mediated bone resorption. In addition to their antiresorptive effects, preclinical evidence strongly suggests that nitrogen-containing bisphosphonates exert direct and indirect anticancer activities through inhibition of tumor cell functions, enhancement of the cytotoxic activity of chemotherapy agents, inhibition of tumor angiogenesis, and stimulation of antitumor immune reactions. This review examines the current evidence and provides insights into ongoing preclinical research on anticancer activities of these bisphosphonates in animal models of tumorigenesis and metastasis.     

Bisphosphonates and implants

The Canadian Joint Replacement Registry (CJRR) was launched in 2000 through the collaborative efforts of the Canadian Orthopedic Association and the Canadian Institutes for Health Information. Participation is voluntary, and data collected by participating surgeons in the operating room is linked to hospital stay information from administrative databases to compile yearly reports. In the fiscal year 2006–2007, there were 62,196 hospitalizations for hip and knee replacements in Canada, excluding Quebec. This represents a 10-year increase of 101% and a 1-year increase of 6%. Compared to men, Canadian women have higher age-adjusted rates per 105 for both TKA (148 vs. 110) and THA (86 vs. 76). There also exist substantial inter-provincial variations in both age-adjusted rates of arthroplasty and implant utilization that cannot be explained entirely on the basis of differing patient demographics. The reasons for these variations are unclear, but probably represent such factors as differences in provincial health expenditure, efforts to reduce waiting lists, and surgeon preference. The main challenge currently facing the CJRR is to increase procedure capture to > 90%. This is being pursued through a combination of efforts including simplification of the consent process, streamlining of the data collection form, and the production of customized reports with information that has direct clinical relevance for surgeons and administrators. As the CJRR continues to mature, we are optimistic that it will provide clinically important information on the wide range of factors that affect arthroplasty outcome.     

Bisphosphonates in phenytoin-induced bone disorder

Chronic administration of phenytoin (PHT) has been associated with bone loss. Bisphosphonates [alendronate (ALD), ibandronate (IBD) and risedronate (RSD)] are potential candidates to prevent PHT-induced bone disorders, and the present study evaluated their effect on the antiepileptic efficacy of PHT. The PHT-induced depletion in folic acid (FA), vitamin B6 and vitamin B12 results in hyperhomocysteinemia. The elevated circulating homocysteine (hcy) could be a risk indicator for micronutrient-deficiency-related osteoporosis via generation of free radicals. Thus, an attempt was also made to unravel the PHT's and bisphosphonates' effect on hcy. Male mice received PHT (35 mg/kg, p.o.) for 90 days to induce bone loss. ALD, RSD and IBD were administered orally at doses 0.65 mg/kg, 0.33 mg/kg, and 0.17 mg/kg respectively, for prevention and 1.3mg/kg, 0.65 mg/kg, and 0.33 mg/kg respectively, for treatment of PHT-induced bone loss. The bone loss was confirmed by bone mineral density (BMD) analysis and bone turnover markers. Serum levels of hcy and FA were estimated along with hydrogen peroxide levels and total antioxidant capacity in order to assess the antioxidant profile of bisphosphonates. The induction of bone loss by PHT was marked by lowered BMD and altered bone turnovers. ALD and RSD administration to PHT treated groups significantly reverted the bony adverse effects. No such effects were observed with IBD. In the bisphosphonates treated groups, hcy levels were statistically at par with the control group. PHT at 35 mg/kg, p.o. could compromise bone mass and thus, could be a model of bone demineralization in mice. The ALD, IBD and RSD have no pharmacodynamic interaction when administered along with PHT at the experimental level. Thus, their usage in the management of PHT-induced bone disease could be worthwhile if clinically approved.     

Bisphosphonates in the renal patient.

Over the past decade, bisphosphonate use in patients with variousforms of kidney disease has become widespread. The extensivetake up-of these agents by nephrologists reflects the twin perceptionsthat bisphosphonates are generally safe in patients with kidneydisease, and that skeletal protection, readily demonstrablein bisphosphonate-treated populations without kidney disease,is also achievable in patients with chronic kidney disease (CKD)and other forms of nephropathy. Unfortunately, both of theseperceptions are based on limited evidence and somewhat tenuousextrapolations [1,2].