Recombinant hormones in osteoporosis

Introduction: For the last 10 years, bone anabolic therapy with the recombinant human parathyroid hormone (rhPTH) analogue, teriparatide (rhPTH[1 – 34]), or full-length rhPTH(1 – 84) has been an option in the treatment of osteoporosis. Both drugs are given as a daily subcutaneous injection. In the USA, only teriparatide is marketed.

Areas covered: Mechanisms of action by which rhPTH induces bone anabolic effects includes changes in bone remodeling, geometry and mineral density. Data from randomized controlled trials on anti-fracture efficacy are reviewed as well as results from a number of recent studies on administration less than once-a-day or intermittent-/cyclic-therapy. Treatment effects are compared with those of anti-resorptive agents.

Expert opinion: In terms of anti-fracture efficacy, treatment with rhPTH is not superior to treatment with potent anti-resorptive agents. However, while the process by which osteoporosis emerges is arrested in response to anti-resorptives, rhPTH acts as a bone anabolic with reversal of the process. Although this mechanism of action seems favorable, the use of rhPTH is limited by a much higher cost than that of anti-resorptive agents. As long as a superior anti-fracture efficacy has not been proven, rhPTH should be confined to patients with severe spinal osteoporosis, including patients in whom treatment with an anti-resorptive has failed.     

Natpara for the treatment of hypoparathyroidism

ABSTRACT

Introduction: Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcaemia and hyperphosphatemia, due to absent or inappropriately low parathyroid hormone levels. For management of chronic hypoparathyroidism, current treatment options involve oral calcium and vitamin D. This standard treatment cannot resolve all problematic aspects of the disease, such as abnormal bone remodeling and reduced quality of life, and is associated with long-term complications, including nephrolithiasis, nephrocalcinosis, renal impairment, cataracts and cerebral calcifications.

Areas covered: In 2015, the FDA (Food and Drug Administration) approved rhPTH (1–84), named Natpara®, a bioengineered recombinant human PTH, for the management of hypoparathyroidism of any etiology, except Autosomal Dominant Hypocalcemia, not well controlled with calcium and active vitamin D. Herein, the authors review its chemistry, pharmacodynamics, pharmacokinetics and clinical efficacy for hypoparathyroidism.

Expert opinion: Replacement therapy with rhPTH (1–84) is a fundamental step in the treatment of chronic hypoparathyroidism in cases not well controlled by standard therapy, providing the natural hormone that is lacking for the maintenance of normal calcium levels, and reducing long-term risks associated with conventional therapy. Nevertheless, given the chronic nature of the disease, in the future, further studies will have to be performed to evaluate long-term efficacy and safety of the drug.     

Denosumab – an emerging treatment for postmenopausal osteoporosis

Importance of the field: Osteoporosis is a common skeletal disease that is associated with an imbalance in bone remodeling. Denosumab is an investigational fully human monoclonal antibody to receptor activator of NF-κB ligand (RANKL), a cytokine member of the TNF family that is the principal mediator of osteoclastic bone resorption.

Areas covered in this review: The efficacy and safety of denosumab in the management of postmenopausal osteoporosis is evaluated by reviewing the published literature and presentations at scientific meetings through 2009.

What the reader will gain: This review focuses on the data on fracture risk reduction and safety endpoints of denosumab in the treatment of postmenopausal osteoporosis.

Take home message: In postmenopausal women with osteoporosis, denosumab (60 mg by subcutaneous injection every 6 months) increased bone mineral density, reduced bone turnover markers, and reduced the risk of vertebral, hip and non-vertebral fractures. Denosumab was well tolerated with a safety profile generally similar to placebo. It is a promising emerging drug for the prevention and treatment of postmenopausal osteoporosis.     

Short-term teriparatide treatment does not affect NT-proBNP,a marker of cardiac disease

Background. Teriparatide (Parathyroid hormone (PTH) 1–34) has been shown to increase bone mineral density (BMD) and reduce the risk of vertebral fractures when given intermittently. In contrast primary hyperparathyroidism (PHPT) is associated with increased bone loss. Moreover an increased occurrence of cardiovascular disease (CVD) is seen in PHPT patients. The N-terminal fragment of the pro-peptide of Brain Natriuretic peptide (NT-proBNP), a risk marker of CVD, has been shown to be elevated in PHPT patients, indicating that continuously high concentrations of PTH affect the heart. Therefore the aim of this study was to investigate whether teriparatide treatment is associated with changes in plasma NT-proBNP. Methods. A total of 42 patients receiving teriparatide treatment were included in the study. Blood samples were taken at baseline, and after 1, 3 and 6 months of treatment. Plasma concentrations of NT-proBNP were measured. Plasma concentrations of ionized calcium, PTH and alkaline phosphatase (ALP) were also analyzed, and BMD for the lumbar spine and total hip was recorded at baseline and after 6 months. Results. Data from 10 men and 32 women, mean age 68 years, were included in the analysis. No effect of teriparatide on plasma concentrations of NT-proBNP was observed at any time points. Ionized calcium and ALP concentrations in the plasma increased after 6 months of treatment, whereas PTH concentrations decreased. Spine BMD T-score was significantly increased after 6 months of treatment. Conclusion. After 6 months of treatment with teriparatide, it did not change the concentration of NT-proBNP in plasma, suggesting that intermittent exposure to therapeutic levels of teriparatide does not affect heart function.     

Romosozumab for the treatment of osteoporosis

Introduction: Sclerostin, a glycoprotein produced primarily by osteocytes, blocks the canonical Wnt signaling bone formation pathway. Romosozumab is a humanized monoclonal antibody to sclerostin that binds to sclerostin, permitting the engagement of Wnt ligands with their co-receptors, resulting in an increase in bone formation and bone mineral density (BMD). Clinical studies with romosozumab have shown dramatic improvements in BMD at the spine and hip. Romosozumab is associated with improvement in bone strength through mechanisms that include increases in bone formation and, different from classical osteoanabolic agents, suppression of bone resorption.

Areas covered: Herein, the authors highlight the available data on romosozumab for the treatment of osteoporosis. This includes the latest data on the efficacy, pharmacokinetics and pharmacodynamics as well as safety and tolerability data.

Expert opinion: Monthly subcutaneous dosing of romosozumab reduces the risk of vertebral and clinical fractures in women with postmenopausal osteoporosis, with a favorable balance of benefits and risks. Romosozumab is a promising emerging anabolic agent with a novel mechanism of action that may expand the options for treating osteoporotic patients at high risk of fracture.     

甲状旁腺激素预防和治疗绝经后骨质疏松症疗效的系统评价

目的系统评价甲状旁腺激素（PTH）预防和治疗绝经后骨质疏松症的疗效和安全性。方法计算机检索MEDLINE（1966～2008．3）、EMBASE（1974—2008．3）、Cochrane图书馆临床试验资料库（2008年第1期）、Current Controlled Trials、The National Reseach Register、中国生物医学文献数据库（1983—2008．3）、中国期刊全文数据库（1994～2008．3），并手工检索相关领域其它杂志。检索不受语种限制，时间截至2008年3月。纳入以患原发性质疏松症或骨量减少的绝经后女性为研究对象、比较甲状旁腺激素与其它疗法疗效的随机对照试验，评价纳入研究的质量，并用RevMan4．2．10软件进行Meta分析。结果共纳入12个随机对照试验，包括5550例患者。Meta分析结果显示：PTH单用或与其它药物联用与对照组比较，减少椎体骨折风险达66％[RR=0．34，95％CI（0．26，0．45），P〈0．00001]；增加腰椎[SMD=0．41，95％CI（0．19，O．63），P=0．0003]和股骨颈[SMD=0．19，95％CI（0．10，0．28），P〈0．0001]的骨密度优于对照组。PTH发生副作用导致的退出和失访多于对照组[Peto—OR=1．69，95% CI（1．39，2．05），P〈0．00001]。结论PTH预防和治疗绝经后骨质疏松症疗效肯定，能提高腰椎及股骨颈的骨密度，降低椎体骨折的风险。PFH对绝经后骨质疏松症的疗效优于阿伦磷酸盐，但不宜和阿伦磷酸盐联合使用，骨量严重低下和有骨质疏松性骨折的绝经后女性是PTH较适合的人群。     

Monoclonal antibodies for the treatment of osteoporosis

Introduction: Osteoporosis is a systemic skeletal disorder that weakens bones and increases the risk of fractures. It is caused by perturbations of bone remodeling, the coupled process whereby bone is continually resorbed and formed in small discrete units. Despite the availability of cost-effective pharmacological agents that reduce fracture risk, many patients who could benefit from treatment are not receiving it. Advances in the understanding of the molecular regulators of bone remodeling have led to the identification of new targets for therapeutic intervention. Monoclonal antibodies directed to these targets have recently been developed, providing new ways of modulating bone remodeling that may provide additional benefits beyond previously available therapy.

Areas covered: An approved fully human monoclonal antibody to receptor activator of nuclear factor-κB ligand, the principal regulator of osteoclastic bone resorption, reduces the risk of fractures in postmenopausal women with osteoporosis. Monoclonal antibodies in development include inhibitors of sclerostin and Dickhopf1, with osteoanabolic activity that may be beneficial in the treatment of osteoporosis.

Expert opinion: Monoclonal antibodies to molecular regulators of bone remodeling represent a new class of compounds for the management of osteoporosis and other skeletal disorders associated with an imbalance of bone resorption and formation.     

The effect of whole-body vibration therapy on bone metabolism,motor function,and anthropometric parameters in women with postmenopausal osteoporosis

Purpose: To review the research literature on the effectiveness of whole-body vibration (WBV) therapy in women with postmenopausal osteoporosis.

Methods: A systematic review was conducted by two independent reviewers. Mean differences (MDs), standardized mean differences (SMDs), and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed with the I² test. The Cochrane risk of bias tool was used to assess the methodological quality of the selected studies.

Results: Nine randomized controlled trials involving 625 patients met the inclusion criteria. No significant improvement was found in bone mineral density (BMD) (SMD?=??0.06, 95%CI=??0.22–0.11, p?=?0.50); bone turnover markers (MD?=??0.25, 95%CI=??0.54–0.03, p?=?0.08); anthropometric parameters, including muscle mass, fat mass, body mass index (BMI), and weight (SMD?=?0.02, 95%CI=??0.16–0.21, p?=?0.81); or maximal isotonic knee extensor strength (SMD?=?0.16, 95%CI=??0.63–0.95, p?=?0.69). However, maximal isometric knee extensor strength improved (SMD?=?0.71, 95%CI?=?0.34–1.08, p?=?0.0002).

Conclusions: WBV is beneficial for enhancing maximal isometric knee extensor strength, but it has no overall treatment effect on BMD, bone turnover markers, anthropometric parameters, or maximal isotonic knee extensor strength in women with postmenopausal osteoporosis.

• Implication of rehabilitation

• Osteoporosis is the leading underlying cause of fractures in postmenopausal women, whole body vibration (WBV) has received much attention as a potential intervention for the management of osteoporosis in recent years.

• Whole body vibration is beneficial for enhancing maximal isometric knee extensor strength in women with postmenopausal osteoporosis.

• Whole body vibration has no overall treatment effect on bone mineral density, bone turnover markers, anthropometric parameters and maximal isotonic knee extensor strength in women with postmenopausal osteoporosis.

     

Effects of Parity and Breastfeeding Duration on Bone Density in Postmenopausal Women

PurposeThis study aimed to identify the effect of parity and breastfeeding duration and the occurrence of lumbar vertebral and femoral neck osteoporosis in Korean postmenopausal women.MethodsThis study analyzed the data of 1,770 women based on the 2010–2011 results of the Korea National Health and Nutrition Examination Survey. Extracted data concerning bone density included variables known to be associated with osteoporosis. Complex sample multivariate logistic regression analysis was conducted to determine whether parity and breastfeeding duration were associated with osteoporosis in postmenopausal women.ResultsParity was not associated with postmenopausal osteoporosis in the femoral neck or lumbar vertebrae; however, the risk of femoral neck osteopenia was significantly higher in women with a history of 12–24 months of breastfeeding than in women who breastfed for less than 12 months (odds ratio = 2.12, 95% confidence interval = 1.07–4.21). In women who breastfed for 24 months or longer, the risk of lumbar vertebral osteoporosis was significantly higher than in those who breastfed for less than 12 months (odds ratio = 2.73, 95% confidence interval = 1.18–6.32).ConclusionBreastfeeding duration may affect the occurrence of lumbar vertebral or femoral neck osteopenia or osteoporosis. Therefore, women who breastfeed for one year or more require education on the risk of bone loss and the need for preventive measures such as adequate calcium intake and physical exercise.     

Risedronate for the prevention of fractures in postmenopausal osteoporosis

OBJECTIVE: To evaluate current scientific literature regarding the efficacy of risedronate in the prevention of vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. DATA SOURCES: Primary research articles were identified by MEDLINE search (1966-May 2001) and through secondary sources. Key search terms were risedronate, postmenopausal osteoporosis, and fractures. DATA SYNTHESIS: Osteoporosis results in a reduction of bone mineral density, increased bone fragility, and increased risk of fractures. The goal of osteoporosis therapy is not only to increase bone mass, but also to reduce the rate of fractures. Risedronate is the newest bisphosphonate to be approved for the prevention and treatment of osteoporosis. An evaluation of clinical trials using risedronate in the treatment of postmenopausal osteoporosis was performed to determine its efficacy at decreasing fracture rates. CONCLUSIONS: Risedronate is an effective and safe option for the treatment of postmenopausal osteoporosis. Risedronate significantly decreases the risk of vertebral and nonvertebral fractures in women who have had > or =1 fractures in the past. More studies are warranted to evaluate the efficacy of risedronate in women without preexisting vertebral fractures.     

Sclerostin monoclonal antibody therapy with AMG 785: a potential treatment for osteoporosis

Importance of the field: Osteoporosis is a common skeletal disease characterized by loss of bone strength that leads to increased risk of fractures. Fractures of the hip and spine are associated with disability, increased risk of death and high healthcare costs. Recent improvement in the understanding of the molecular regulators of bone metabolism has led to the investigation and development of new therapeutic agents with novel mechanisms of action that may offer advantages over currently available treatments for osteoporosis.

Areas covered in this review: Sclerostin is a small protein secreted by osteocytes that downregulates osteoblast-mediated bone formation. This is a review of the rationale, mechanism of action, preclinical and clinical development of AMG 785 (CDP7851), an investigational humanized mAb that inhibits the activity of sclerostin, resulting in increased bone formation.

What the reader will gain: The reader will gain an insight into the potential use of sclerostin mAb therapy for the treatment of osteoporosis.

Take home message: Preclinical studies and an early report of a clinical study suggest that inhibition of sclerostin with AMG 785 may provide skeletal benefit for patients with osteoporosis.     

Mechanisms for the bone anabolic effect of parathyroid hormone treatment in humans

Abstract

Intermittent low-dose treatment with parathyroid hormone (PTH) analogues has become widely used in the treatment of severe osteoporosis. During normal physiological conditions, PTH stimulates both bone formation and resorption, and in patients with primary hyperparathyroidism, bone loss is frequent. However, development of the biochemical measurement of PTH in the 1980s led us to understand the regulation of PTH secretion and calcium metabolism which subsequently paved the way for the use of PTH as an anabolic treatment of osteoporosis as, when given intermittently, it has strong anabolic effects in bone. This could not have taken place without the basic understanding achieved by the biochemical measurements of PTH. The stimulatory effects of PTH on bone formation have been explained by the so-called ‘anabolic window’, which means that during PTH treatment, bone formation is in excess over bone resorption during the first 6–18 months. This is due to the following: (1) PTH up-regulates c-fos expression in bone cells, (2) IGF is essential for PTH's anabolic effect, (3) bone lining cells are driven to differentiate into osteoblasts, (4) mesenchymal stem cells adhesion to bone surface is enhanced, (5) PTH has a direct antiapoptotic effect on osteoblasts and (6) when PTH interferes with remodelling, the osteoblasts over-compensate, and (7) PTH also decreases sclerostin levels, thereby removing inhibition of Wnt signalling which is required for PTH's anabolic actions. Thus, the net formative effect of PTH given in intermittent treatment emerges through a complex network of pathways. In summary, the effects of PTH on bone turnover are dependent on the mode and dose of administration and studies investigating the mechanisms underlying this effect are reviewed in this article.     

Reduced bone mass and increased bone turnover in postmenopausal women with epilepsy using antiepileptic drug monotherapy

Objectives. The aims of this study were to assess the occurrence of osteoporosis and fracture rate in Norwegian postmenopausal women with epilepsy using antiepileptic drugs (AEDs), and to investigate how AEDs may affect bone health. Material and methods. Twenty‐six female patients receiving AED monotherapy and 26 individually matched healthy controls answered questions about their general health, lifestyle and previous fractures. For both groups, bone mineral density (BMD) was measured by DEXA, and serum samples were analysed for biochemical bone turnover markers and haematological parameters. Results. The patients, particularly those treated with enzyme‐inducing AEDs, had significantly lower BMD than the controls. Additionally, 62?% of the women with epilepsy had osteoporotic T‐values in one or more regions, compared with 27?% in the control group. There was a non‐significant tendency towards an increased fracture rate among the patients. Markers for bone formation (ALP, bALP, osteocalcin) and bone resorption (Crosslaps) were elevated in the patient group compared with the controls. Conclusions. Compared with the healthy controls, we found an increased occurrence of osteoporosis, probably due to increased bone turnover, among Norwegian postmenopausal women with epilepsy undergoing AED monotherapy, which may render these women especially vulnerable to fractures.     

RISEDRONATE: CLINICAL USAGE

Risedronate is a new bisphosphonate – a family of drugs that inhibit bone resorption – and thus can be used in various bone conditions involving increased levels of bone resorption, such as postmenopausal osteoporosis, glucocorticoid-induced bone loss, and Paget's disease of bone. In placebo-controlled clinical trials, risedronate has been shown to prevent bone loss in postmenopausal women, to decrease the incidence of vertebral and non vertebral (including hip) fractures in postmenopausal women with osteoporosis, and to prevent bone loss in men and women treated with moderate to high doses of glucocorticoids. Risedronate has also been shown substantially to decrease the severity of bone pain and the level of bone turnover in Paget's disease of bone, and to improve the radiographic lesions of this disease. Risedronate is safe and well tolerated. Thus, risedronate is a new option for the management of postmenopausal osteoporosis, Paget's disease of bone and corticosteroid-induced bone loss.     

Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in a Subset of Younger Postmenopausal Women with Osteoporosis at High Risk for Fracture

PurposeCurrent treatment guidelines recommend treatment for postmenopausal women with a T score <−2.5 regardless of age. This subgroup analysis evaluated the efficacy and safety of abaloparatide in younger postmenopausal women considered to be at high risk for fracture.MethodsSubgroup analysis of women in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial who were <65 years old and met modified utilization management criteria (baseline T score ≤−2.5 [any site] and ≥1 prevalent vertebral and/or ≥1 prior clinical fracture within 5 years of randomization).FindingsA total of 296 women (age range, 49–64 years) were included. Significant increases in bone mineral density from baseline were observed for abaloparatide versus placebo at all 3 sites at 6 months (p < 0.01 for total hip and femoral neck; p < 0.0001 for lumbar spine), 12 months (p < 0.0001 at all 3 sites), and 18 months (p < 0.0001 at all 3 sites). Fracture rates were numerically lower for abaloparatide versus placebo, consistent with the overall trial results, although the differences were not statistically significant. The number needed to treat to prevent 1 additional vertebral fracture after 18 months of treatment versus placebo was 18 for abaloparatide and 21 for teriparatide. The number needed to treat had nonsignificant trends toward lower values with abaloparatide versus teriparatide for nonvertebral fractures (23 vs 40) and clinical fractures (16 vs 73) and similar for major osteoporotic fractures (24 vs 27). The safety profile was consistent with the overall ACTIVE population.ImplicationsFindings of this subgroup (post hoc) analysis are consistent with the overall ACTIVE population. Abaloparatide appears to be effective and well tolerated in this subgroup of younger postmenopausal women. ClinicalTrials.gov identifier: NCT01343004.     

骨密度影像学测量与椎体骨折率评估结合提高骨质疏松的诊断率

背景：临床上用于诊断骨质疏松症的通用指标：脆性骨折或骨密度 T ≤-2.5标准差,只要满足一个条件即可作出骨质疏松的诊断。在做骨密度检查时同时进行椎体骨折评估,可以避免单一因素的评判造成骨质疏松症的漏诊,有利于提高骨质疏松的诊断率。目的：评估骨密度结合椎体骨折对骨质疏松症临床诊断率的影响。方法：对217例年龄≥50岁的绝经后女性患者行髋部骨密度检测,同时进行椎体骨折评估,比较单纯依靠骨密度检查与骨密度结合椎体骨折评估对骨质疏松的诊断率的影响,同时探讨骨密度对椎体骨折率的影响。结果与结论：92例骨密度T ≤-2.5,达到骨质疏松诊断阈值,占42.4%;102例骨密度-1〉 T 〉-2.5,为低骨量,占47.0%;23例骨密度在正常范围,骨密度T〉-1,占10.6%。158例无椎体骨折;59例（27.2%）椎体骨折,101个骨折椎。骨密度T〉-2.5的患者椎体骨折率为21.6%,骨密度T ≤-2.5的患者椎体骨折率34.8%,两组骨折率比较差异有显著性意义（P 〈0.05）;骨密度结合椎体骨折评估的骨质疏松诊断率为54.8%,比单纯依靠骨密度检查,骨质疏松诊断率提高12.4%（P=0.01）。说明绝经后女性做骨密度检测的同时进行椎体骨折评估可以提高骨质疏松的诊断率。     

Parathyroid hormone (1-84) and treatment of osteoporosis

OBJECTIVE: To present the chemistry, pharmacology, and pharmacokinetics of parathyroid hormone (PTH) (1-84) and review the available clinical trials that evaluate its efficacy and safety; clinical applicability of this agent and its relationship to other Food and Drug Administration (FDA)-approved medications for treatment of osteoporosis are also discussed. DATA SOURCES: A MEDLINE search (1996-December 2004) was completed, along with a review of information obtained from the manufacturer, NPS Pharmaceuticals. Key search terms included parathyroid hormone, PTH (1-84), and ALX 111. STUDY SELECTION AND DATA EXTRACTION: Studies were selected based on their relevance and availability. Pertinent information, including objectives, design, demographics, outcomes, adverse events, dosing strategies, and therapeutic controversies, was extracted. DATA SYNTHESIS: PTH (1-84) is being developed for treatment of osteoporosis. Recent studies have shown that, when administered intermittently as a subcutaneous injection, PTH (1-84) produces an increase in bone mineral density and prevents vertebral fractures. The fact that this agent contains the C-terminal region of PTH may differentiate it from PTH (1-34), teriparatide, which is approved by the FDA for treatment of osteoporosis. Further trials are necessary to determine the role of PTH (1-84) in combination with other treatments for osteoporosis and/or the order in which PTH (1-84) is given with these other agents. There are currently no comparative trials with other osteoporosis treatment modalities. CONCLUSIONS: PTH (1-84), when given intermittently as a subcutaneous injection, appears to be a safe and efficacious treatment option for osteoporosis. Further trials are needed to determine its specific place in therapy compared with other treatment options.     

The relationship between intact PTH and biointact PTH (1–84) with bone and mineral metabolism in pre-dialysis chronic kidney disease (CKD)

Objectives

Abnormalities in PTH are implicated in the pathogenesis of bone abnormalities in chronic kidney disease (CKD)–mineral bone disorder (CKD–MBD). PTH concentrations are important in clinical decision and management. This emphasises the importance of providing an assay which measures biologically active PTH. We compared concentrations of intact PTH with biointact PTH (1–84) in CKD and end stage renal disease (ESRD) and investigated the relationship between the 2 PTH assays with bone and mineral laboratory parameters and bone mineral density (BMD) in CKD.

Design and methods

We assessed 140 patients (61 in ESRD and 79 with CKD stages 1–4) in this cross-sectional study. We measured biointact PTH (1–84) as well as routine biochemical parameters on all subjects. In the CKD cohort, bone turnover markers; bone alkaline phosphatase (BAP) and tartrate resistant acid phosphatase (TRACP)-5b and bone mineral density (BMD) were also determined.

Results

In ESRD, intact PTH concentration was significantly higher compared to biointact PTH (1–84) (422 [443] v/s 266 [251] pg/mL, (p < 0.001) with an average bias of 60%. In CKD, intact PTH concentration was also higher compared to biointact PTH (1–84) (79[55] v/s 68[49] pg/mL p < 0.001) with an average bias of 18%. Only the biointact PTH (1–84) assay showed any significant correlation with serum calcium concentrations (r = − 0.26, p < 0.05) and phosphate (r = 0.25, p < 0.05) in CKD. Following multilinear regression analysis and adjustment for all significant co-variables, only eGFR, BAP and 25 (OH)vitamin remained significantly associated with intact PTH and biointact PTH (1–84). The strength of association was stronger between BAP and biointact PTH (1–84) (biointact PTH (1–84): p = 0.007, intact PTH: p = 0.01). In adjusted analyses, only biointact PTH (1–84) was significantly associated with BMD at the fore-arm (FARM) (p = 0.049).

Conclusions

The study confirms the differences between intact PTH and biointact PTH (1–84) in ESRD. Whilst there may be similarities in the diagnostic ability of both intact and biointact PTH (1–84), our data suggest that biointact PTH (1–84) assay may better reflect bone metabolism and BMD in CKD. Further longitudinal studies are needed.     

Gastric Vagotomy in Peptic Ulcer

PREVIEW

Osteoporosis is considered a disorder of postmenopausal women because bone mineral loss and accompanying fragility fractures are common in this group. However, certain premenopausal women are also at risk for osteoporosis. Because of a lack of screening and treatment guidelines for premenopausal women, it can be difficult to determine whether a low bone mineral density correlates with a disease such as osteoporosis and to predict the potential risk of a fracture and formulate the correct course of action. In this article, Dr Derk identifies high-risk groups, presents an approach to judicious screening, and recommends prevention and treatment strategies.     

Clinical evaluation of two novel biointact PTH(1–84) assays in hemodialysis patients

Objectives

In chronic kidney disease–mineral and bone disorder (CKD-MBD), most treatment decisions are guided by parathyroid hormone (PTH) levels. Here, we aimed at assessing the technical and clinical performance of two novel automated biointact PTH(1–84) assays, from Roche Diagnostics (Ro) and DiaSorin (DS), in hemodialysis patients.

Design and methods

We recorded demographics, dialysis treatment characteristics, pharmacotherapy for CKD-MBD and laboratory work-up. Statistical methods included Passing–Bablok, and multiple linear regression.

Results

121 patients, dialyzing on average for 3.5 years (range: 0.1–22.5), with serum phosphate 1.9 ± 0.6 mmol/L (mean ± SD), participated in the study. Median serum concentration for intact PTH was 223 ng/L (range: 5–2844), and for biointact PTH(1–84) was 136 ng/L (Ro; range: 1–1644), respectively 138 ng/L (DS; range: 4-1580). Both biointact assays were significantly correlated (r = 0.98; Ro = 0.87 × DS + 19.60). Bland–Altmann plots revealed an average bias ± 2 SD of 10 ± 27 ng/L below 200 ng/L, and − 32 ± 157 ng/L above 200 ng/L (Ro minus DS). The variably adjusted association between PTH and serum phosphate was very similar, regardless of the PTH assay, but this was not the case for PTH-derived measures (ratios biointact/intact; differences intact minus biointact). (Log)PTH concentrations as well as serum phosphate were significantly associated with serum creatinine, but only in patients with > 0 mL urine per day.

Conclusions

Results from Roche and DiaSorin biointact PTH(1–84) assays were well correlated, but showed increased deviations at higher concentrations. Biointact PTH(1–84) levels are roughly two third of intact PTH. The association between PTH and serum creatinine may depend on residual renal clearance of PTH and/or serum phosphate.