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1.  Surgical approach to bone healing in osteoporosis 
Osteoporotic fractures represent one of the most common cause of disability and one of the major voice in the health economic budget in many countries of the world. Fragility fractures are especially meta-epiphyseal fractures, in skeletal sites with particular biomechanic characteristic (hip, vertebrae), complex and with more fragments, with slow healing process (mineralization and remodeling) and co-morbidity. The healing of a fracture in osteoporotic bone passes through the normal stages and concludes with union of the fracture although the healing process is prolonged. Fractures in the elderly osteoporotic patients represent a challenge to the orthopaedic surgeons. Osteoporosis does not only increase the risk of fracture but also represents a problem in osteofixation of fractures in fracture treatment. The major technical problem that surgeons face, is the difficulty to obtain a stable fixation of an implant due to osteoporotic bone. The load transmitted at the bone-implant interface can often exceed the reduced strain tolerance of osteoporotic bone.
In the treatment of osteoporotic fractures it is important to consider different aspects: general conditions of elderly patient and comorbidity, the reduced muscular and bone mass and the increased bone fragility, structural modifications as medullary expansion.
The aim of surgical treatment is to obtain a stable fixation that reduces pain and permits an early mobilization.
PMCID: PMC2781233  PMID: 22461162
osteoporosis, bone healing, fractures fixation.
2.  Clinical and surgical approach of severe bone fragility fracture: clinical case of 4 fragility fracture in patient with heavy osteoporosis 
Summary
An accurate diagnosis of osteoporosis and a proper treatment are today recognized to be the most important facts for prevention and for a correct arrangement and treatment of fragility fractures. In the text the Authors describe a case of severe osteoporosis aggravated by 2 femur fractures and 2 periprosthetic fractures occurred in 2 months. In such cases the orthopaedic surgeon needs to formulate first a clinical osteoporotic pattern, than its treatment together with a surgery suitable choice, that has to take into consideration of the bone structural characteristics. In the case described one can note that fractures healing occurred thanks to both an improvement in surgical techniques and antiosteoporotic pharmacological support; in the specific case the Authors used strontium ranelate for its osteoinductive capacity. In our opinion is crucial that the treatment used by orthopaedic surgeons is not related only to the “by-hand” treatment but take into consideration both the underlying disease and the possibility of positively affect bone healing with specific drug therapy.
doi:10.11138/ccmbm/2013.10.1.052
PMCID: PMC3710011  PMID: 23858312
osteoporosis; periprosthetic fractures; bone healing
3.  Knowledge of orthopaedic surgeons in managing patients with fragility fracture 
International Orthopaedics  2012;36(6):1275-1279.
Purpose
Fragility fractures represent a major health problem, as they cause deformity, disability and increased mortality rates. Orthopaedic surgeons should identify patients with fragility fractures and manage their osteoporosis in order to reduce the risk of future fracture; therefore, orthopaedic surgeons’ knowledge about managing fragile fracture should be evaluated.
Methods
A questionnaire was administered to 2,910 orthopaedic surgeons to address the respondents’ knowledge. The questions covered the topics of diagnosis, treatment and approach to a patient with a fragility fracture. The data-collection period for this survey spanned one year.
Results
There were 2,021 orthopaedic surgeons who participated in this study. Less than 10% of the respondents included bone mass densitometry (BMD) when evaluating patients with fragile fractures 32% prescribed proper dosage of calcium and vitamin D; approximately 30% would refer if falling from a height was suspected.
Conclusions
The majority of orthopaedic surgeons questioned lacked knowledge of fragility fracture management. This is reflected by limited knowledge of osteoporosis assessment and treatment in most areas. An appropriate method should be created to manage patients with fragility fractures to guarantee the patient the best possible care.
doi:10.1007/s00264-012-1482-0
PMCID: PMC3353064  PMID: 22281934
4.  Surgical Treatment of Osteopetrosis-Related Femoral Fractures: Two Case Reports and Literature Review 
Case Reports in Orthopedics  2014;2014:891963.
Osteopetrosis is a rare hereditary disease which is characterized by increased bone density. Bone resorption is insufficient or fails due to the osteoclast defect in osteopetrosis. Half of the patients are asymptomatic and diagnosed incidentally or based on the presence of fracture. Adult onset osteopetrosis usually presents with hip and proximal femoral fractures. Internal fixation can be performed; however, technical challenges may be experienced due to increased bone density. As in other fractures, nonunion or varus malunion of these fractures may occur. Although rare, osteopetrosis may complicate treatment of fractures in such patients. In this study, we aimed to present two new cases of ADO type II with an osteopetrotic femoral fracture along with the clinical and radiological findings in the light of a comprehensive literature review. Orthopaedics surgeons should be aware of intraoperative technical difficulties and possible postoperative complications during the follow-up period. Investigation would be beneficial for the diagnosis of osteopetrosis such the patient with fractures who has minor trauma history and increased bone density in radiography.
doi:10.1155/2014/891963
PMCID: PMC3918852  PMID: 24579054
5.  Optimizing Screening for Osteoporosis in Patients With Fragility Hip Fracture 
Background
Osteoporosis, the underlying cause of most hip fractures, is underdiagnosed and undertreated. The 2008 Joint Commission report Improving and Measuring Osteoporosis Management showed only an average of 20% of patients with low-impact fracture are ever tested or treated for osteoporosis. We developed an integrated model utilizing hospitalists and orthopaedic surgeons to improve care of osteoporosis in patients with hip fracture.
Questions/purposes
Does our integrated model combining hospitalists and orthopaedic surgeons improve the frequency of evaluation for osteoporosis, screening for secondary causes, and patients’ education on osteoporosis?
Patients and Methods
Our Hospitalist-Orthopaedic Surgeon Integrated Model of Care was implemented in September 2009. We compared the rate of evaluation and treatment of osteoporosis in 140 patients admitted with fragility hip fracture at our institution before (70 patients) and after (70 patients) implementation of the care plan.
Results
Evaluation of patients for osteoporosis was higher in the postimplementation group compared to the preimplementation group (89% versus 24%). Screening of patients for secondary causes of osteoporosis was also improved in the postimplementation group (89% versus 0%), as was the proportion of patients who received education for osteoporosis management (89% versus 0%).
Conclusion
Our model of integrated care by hospitalists and orthopaedic surgeons resulted in improvement in the evaluation for osteoporosis, screening for secondary causes of osteoporosis, and education on osteoporosis management in patients with hip fracture at our institution. This may have important implications for treatment of these patients.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-011-1839-5
PMCID: PMC3111791  PMID: 21387105
6.  Bisphophonates in CKD Patients with Low Bone Mineral Density 
The Scientific World Journal  2013;2013:837573.
Patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) have a high risk of bone fracture because of low bone mineral density and poor bone quality. Osteoporosis also features low bone mass, disarranged microarchitecture, and skeletal fragility, and differentiating between osteoporosis and CKD-MBD in low bone mineral density is a challenge and usually achieved by bone biopsy. Bisphosphonates can be safe and beneficial for patients with a glomerular filtration rate of 30 mL/min or higher, but prescribing bisphosphonates in advanced CKD requires caution because of the increased possibility of low bone turnover disorders such as osteomalacia, mixed uremic osteodystrophy, and adynamic bone, even aggravating hyperparathyroidism. Therefore, bone biopsy in advanced CKD is an important consideration before prescribing bisphosphonates. Treatment also may induce hypocalcemia in CKD patients with secondary hyperparathyroidism, but vitamin D supplementation may ameliorate this effect. Bisphosphonate treatment can improve both bone mineral density and vascular calcification, but the latter becomes more unlikely in patients with stage 3-4 CKD with vascular calcification but no decreased bone mineral density. Using bisphosphonates requires considerable caution in advanced CKD, and the lack of adequate clinical investigation necessitates more studies regarding its effects on these patients.
doi:10.1155/2013/837573
PMCID: PMC3899701  PMID: 24501586
7.  Assessment of scaphoid fracture healing 
Scaphoid fractures are among the most common hand fractures in adults. The geometry of the scaphoid as it relates to its retrograde blood supply renders it particularly prone to avascular necrosis and other fracture complications. Though there has been long-standing debate over the optimal method of diagnosing scaphoid fractures, the best and most cost-effective methods combine clinical exam with other imaging modalities such as navicular view plain films, CT, and MRI for particularly questionable presentations. Once a scaphoid fracture is diagnosed, it should be followed by an orthopaedic surgeon and treated with cast immobilization or operative management in the case of displaced fractures. Fractures should be followed to monitor healing progress in order to ensure the eventual development of bridging bone across the fracture line, usually best appreciated on CT. Proper treatment of scaphoid fractures and assessment of fracture healing can minimize the occurrence of non-unions and associated arthritic changes.
doi:10.1007/s12178-011-9072-0
PMCID: PMC3070004  PMID: 21475561
Scaphoid fracture; Healing; Imaging; Non-union
8.  Strontium Ranelate: The Pathophysiological Rationale 
Skeletal metabolism and the replacement of damaged tissue with the same amount of intact bone depends on the correct balance between bone formation and bone resorption.
The existence of an imbalance between bone formation and resorption is a concept central to understanding of the pathophysiology of osteoporosis and the reduction of fracture risk.
With aging, the volume of bone that is formed during the bone remodelling process and after injury is less than the volume absorbed during the bone resorption phase; this results in bone loss and increased bone fragility. In addition to bone mineral density, many other properties of bone are determined by the balance between bone formation and bone resorption. A bone that is biomechanically more fragile is also a bone that consolidates more slowly after a fracture event. Although the fracture healing stages are the same even in the presence of osteoporosis, recent studies have shown a slowdown in the process of consolidation when osteoporosis is present. In particular, strategies to reduce fracture risk and facilitate the process of consolidation of the fracture may be a primary criterion for selection.
The ability to modulate anabolic and catabolic phenomena in the skeleton, both locally and systemically, opens up a new horizon for the reduction of fracture risk and the enhancement of bone healing, particularly when the bone is qualitatively and/or quantitatively compromised.
Clinical research has recently allowed the development of therapies, such as treatment with strontium ranelate, able to increase production of bone matrix by osteoblasts and to act positively on the distribution of the skeletal microarchitecture. Strontium ranelate is able to rebalance bone turnover in favour of the formation of more resistant and elastic bone, by stimulating osteoblasts and inhibiting the resorptive activity of osteoclasts, thereby ensuring rapid and lasting protection against the risk of fractures. In vitro studies have shown that the drug is able to promote replication of the first pre-osteoblasts and their differentiation into mature osteoblasts and osteocytes interacting with the receptor CaSR and through the increased synthesis of OPG. Thanks, again, to the participation of the CaSR receptor, but also by reducing the production of RANKL, strontium ranelate decreases the resorptive activity of osteoclasts. The anabolic action of strontium ranelate in terms of mineral apposition rate in both cortical and trabecular bone was demonstrated on bone biopsies analysed by three-dimensional micro-CT. The drug was shown to increase the number of trabeculae, the cortical thickness, and the total bone volume. The bone-forming activity of strontium ranelate was also demonstrated in comparative studies versus teriparatide and antiresorptive agents. In experimental studies the bone-forming effect of strontium ranelate leads to an increase in the bone callus volume and its maturation and, in turn, to an acceleration of the consolidation of the fracture and better implant osteointegration.
In conclusion, the mechanism of action of strontium ranelate, which inhibits bone resorption in favour of new bone formation, is able to counteract, in a physiological manner, the bone loss associated with advancing age. The net effect is an increase in bone mass, trabecular and cortical bone, which explains its anti-fracture efficacy. The drug’s ability to stimulate bone formation seems to unfold at the level of the callus allowing improved fracture healing and in the case of implants potential improvement of implant osteointegration.
PMCID: PMC3213810
9.  Breakout Session: Sex/Gender and Racial/Ethnic Disparities in the Care of Osteoporosis and Fragility Fractures 
Background
Recent epidemiologic and clinical data suggest men and racial and ethnic minorities may receive lower-quality care for osteoporosis and fragility fractures than female and nonminority patients. The causes of such differences and optimal strategies for their reduction are unknown.
Questions/purposes
A panel was convened at the May 2010 American Academy of Orthopaedic Surgeons/Orthopaedic Research Society/Association of Bone and Joint Surgeons Musculoskeletal Healthcare Disparities Research Symposium to (1) assess current understanding of sex/gender and racial/ethnic disparities in the care of osteoporosis and after fragility fractures, (2) define goals for improving the equity and quality of care, and (3) identify strategies for achieving these goals.
Where are we now?
Participants identified shortcomings in the quality of care for osteoporosis and fragility fractures among male and minority populations and affirmed a need for novel strategies to improve the quality and equity of care.
Where do we need to go?
Participants agreed opportunities exist for health professionals to contribute to improved osteoporosis management and secondary fracture prevention. They agreed on a need to define standards of care and management for osteoporosis and fragility fractures and develop strategies to involve physicians and other health professionals in improving care.
How do we get there?
The group proposed strategies to improve the quality and equity of osteoporosis and care after fragility fractures. These included increased patient and physician education, with identification of “champions” for osteoporosis care within and outside of the healthcare workforce; creation of incentives for hospitals and physicians to improve care; and research comparing the effectiveness of approaches to osteoporosis screening and fracture management.
doi:10.1007/s11999-011-1859-1
PMCID: PMC3111803  PMID: 21424834
10.  Bone morphogenetic protein-7 accelerates fracture healing in osteoporotic rats 
Indian Journal of Orthopaedics  2013;47(6):540-546.
Background:
Osteoporosis is characterized by low bone mass, bone fragility and increased susceptibility to fracture. Fracture healing in osteoporosis is delayed and rates of implant failure are high with few biological treatment options available. This study aimed to determine whether a single dose of bone morphogenetic protein-7 (BMP-7) in a collagen/carboxy-methyl cellulose (CMC) composite enhanced fracture healing in an osteoporotic rat model.
Materials and Methods:
An open femoral midshaft osteotomy was performed in female rats 3 months post-ovarectomy. Rats were randomized to receive either BMP-7 composite (n = 30) or composite alone (n = 30) at the fracture site during surgery. Thereafter calluses were collected on days 12, 20 and 31. Callus cross-sectional area, bone mineral density, biomechanical stiffness and maximum torque, radiographic bony union and histological callus maturity were evaluated at each time point.
Results:
There were statistically significant increases in bone mineral density and callus cross-section area at all time points in the BMP-7 group as compared to controls and biomechanical readings showed stronger bones at day 31 in the BMP-7 group. Histological and radiographic evaluation indicated significant acceleration of bony union in the BMP-7 group as compared to controls.
Conclusion:
This study demonstrated that BMP-7 accelerates fracture healing in an oestrogen-deficient environment in a rat femoral fracture healing model to scientific relevance level I. The use of BMP-7 composite could offer orthopedic surgeons an advantage over oestrogen therapy, enhancing osteoporotic fracture healing with a single, locally applied dose at the time of surgery, potentially overcoming delays in healing caused by the osteoporotic state.
doi:10.4103/0019-5413.121569
PMCID: PMC3868133  PMID: 24379457
Bone morphogenetic protein-7; carboxy-methyl cellulose; oestrogen; osteoporotic fracture healing; rat femur
11.  Does osteoporosis increase complication risk in surgical fracture treatment? A protocol combining new endpoints for two prospective multicentre open cohort studies 
Background
With an ever-increasing elderly population, orthopaedic surgeons are faced with treating a high number of fragility fractures. Biomechanical tests have demonstrated the potential role of osteoporosis in the increased risk of fracture fixation complications, yet this has not been sufficiently proven in clinical practice. Based on this knowledge, two clinical studies were designed to investigate the influence of local bone quality on the occurrence of complications in elderly patients with distal radius and proximal humerus fractures treated by open reduction and internal fixation.
Methods/Design
The studies were planned using a prospective multicentre open cohort design and included patients between 50 and 90 years of age. Distal radius and proximal humerus fractures were treated with locking compression 2.4 mm and proximal humerus internal locking plates, respectively. Follow-up examinations were planned for 6 weeks, 3 and 12 months as well as a telephone interview at 6 months. The primary outcome focuses on the occurrence of at least one local bone quality related complication. Local bone quality is determined by measuring bone mineral density and bone mineral content at the contralateral radius. Primary complications are categorised according to predefined factors directly related to the bone/fracture or the implant/surgical technique. Secondary outcomes include the documentation of soft tissue/wound or general/systemic complications, clinical assessment of range of motion, and patient-rated evaluations of upper limb function and quality of life using both objective and subjective measures.
Discussion
The prospective multicentre open cohort studies will determine the value of local bone quality as measured by bone mineral density and content, and compare the quality of local bone of patients who experience a complication (cases) following surgery with that of patients who do not (controls). These measurements are novel and objective alternatives to what is currently used.
Trial registration numbers
Clinical Trials.gov NCT01144208 and NCT01143675
doi:10.1186/1471-2474-11-256
PMCID: PMC2992478  PMID: 21062463
12.  The clinical utility of bone marker measurements in osteoporosis 
Osteoporosis is characterised by low bone mass and structural deterioration of bone tissue, resulting in increased fragility and susceptibility to fracture. Osteoporotic fractures are a significant cause of morbidity and mortality. Direct medical costs from such fractures in the UK are currently estimated at over two billion pounds per year, resulting in a substantial healthcare burden that is expected to rise exponentially due to increasing life expectancy. Currently bone mineral density is the WHO standard for diagnosis of osteoporosis, but poor sensitivity means that potential fractures will be missed if it is used alone. During the past decade considerable progress has been made in the identification and characterisation of specific biomarkers to aid the management of metabolic bone disease. Technological developments have greatly enhanced assay performance producing reliable, rapid, non-invasive cost effective assays with improved sensitivity and specificity. We now have a greater understanding of the need to regulate pre-analytical sample collection to minimise the effects of biological variation. However, bone turnover markers (BTMs) still have limited clinical utility. It is not routinely recommended to use BTMs to select those at risk of fractures, but baseline measurements of resorption markers are useful before commencement of anti-resorptive treatment and can be checked 3–6 months later to monitor response and adherence to treatment. Similarly, formation markers can be used to monitor bone forming agents. BTMs may also be useful when monitoring patients during treatment holidays and aid in the decision as to when therapy should be recommenced. Recent recommendations by the Bone Marker Standards Working Group propose to standardise research and include a specific marker of bone resorption (CTX) and bone formation (P1NP) in all future studies. It is hoped that improved research in turn will lead to optimised markers for the clinical management of osteoporosis and other bone diseases.
doi:10.1186/1479-5876-11-201
PMCID: PMC3765909  PMID: 23984630
Bone turnover markers; Bone formation; Bone resorption; Osteoporosis; Biological variability
13.  Treatment of osteoporosis in men with bisphosphonates: rationale and latest evidence 
Osteoporosis in men contributes to significant morbidity and mortality. Hip fractures in men are associated with greater mortality compared with women, with a mortality rate of up to 37.5% within a year following the fracture. Its timely diagnosis and treatment are therefore essential. However, despite one-third of all hip fractures worldwide occurring in men, osteoporosis in men remains an immensely under-recognized and undertreated public health problem. Bisphosphonates are well studied first-line treatments for postmenopausal women with osteoporosis and have been shown to reduce fragility fractures at all clinically important sites (vertebral, nonvertebral, hip and wrist). However, the majority of studies of oral or intravenous bisphosphonate therapy in men with osteoporosis report effects on surrogate markers, including bone mineral density (BMD) and biochemical bone turnover markers, rather than on fragility fractures. Oral or intravenous bisphosphonate therapy increases spinal, total hip and femoral neck BMD compared with placebo in men with osteoporosis. Both bone resorption and bone formation markers are decreased following bisphosphonate therapy, with the onset of the decrease in bone formation markers being delayed. In a study of intravenous zoledronic acid given to older men and women following a hip fracture, any clinical vertebral and nonvertebral fractures were all reduced compared with placebo infusions. In addition, mortality was reduced in patients who received zoledronic acid.
Recent studies in men with osteoporosis have increasingly reported reductions in incident vertebral fractures with oral or intravenous bisphosphonate therapy, although all studies have been underpowered to detect effects on nonvertebral and hip fracture outcomes. Bisphosphonates have a role as monotherapy, as consolidative therapy after a course of teriparatide therapy, or in combination with testosterone replacement in men with hypogonadism and osteoporosis. Bisphosphonate therapy is validated and important in the treatment of osteoporosis in men.
doi:10.1177/1759720X13500861
PMCID: PMC3791089  PMID: 24101947
alendronate; bisphosphonates; hypogonadism; osteoporosis; risedronate; zoledronic acid
14.  Secondary Prevention of Fragility Fractures: Are We Following the Guidelines? 
INTRODUCTION
The aim of this study was to determine whether orthopaedic surgeons follow the British Orthopaedic Association (BOA) guidelines for secondary prevention of fragility fractures.
PATIENTS AND METHODS
A retrospective audit was conducted on patients with neck of femur fractures treated in our hospital between October and November 2003. A re-audit was conducted during the period August to October 2004.
RESULTS
There were 27 patients in the initial study period. Twenty-six patients (96%)had full blood count measured with LFT and bone-profile measured in 18 patients (66%). Only nine patients (30%)had treatment for osteoporosis (calcium and vitamin D). Only one patient was referred for DEXA scan. Steps were taken in the form of creating better awareness among the junior doctors and nurse practitioners of the BOA guidelines. In patients above 80 years of age, it was decided to use abbreviated mental score above 7 as a clinical criteria for DEXA referral. A hospital protocol based on BOA guidelines was made. A re-audit was conducted during the period August to October 2004. There were 37 patients. All had their full blood count and renal profile checked (100%). The bone-profile was measured in 28 (75.7%) and LFT in 34 (91.9%)patients. Twenty-four patients (65%) received treatment in the form of calcium + vitamin D (20) and bisphosphonate (4). DEXA-scan referral was not indicated in 14 patients as 4 were already on bisphosphonates and for 10 patients their abbreviated mental score was less than 7. Among the remaining 23 patients, 9 patients (40%) were referred for DEXA scan. This improvement is statistically significant (P = 0.03, chi square test).
DISCUSSION AND CONCLUSIONS
The re-audit shows that, although there is an improvement in the situation, we are still below the standards of secondary prevention of fragility fractures with 60% of femoral fragility fracture patients not being referred for DEXA scan. A pathway lead by a fracture liaison nurse dedicated to osteoporotic fracture patients should improve the situation.
doi:10.1308/003588406X116891
PMCID: PMC1964691  PMID: 17002853
Osteoporosis; Secondary prevention; Guidelines
15.  A Fracture Does Not Adversely Affect Bone Mineral Density Responses after Teriparatide Treatment 
Background
Fracture leads to local and systemic catabolic physiologic changes. As teriparatide is an agent used to treat osteoporosis in patients with fragility fractures, it is unclear whether teriparatide treatment alters bone mineral density (BMD) and bone markers when given to patients with fractures.
Questions/purposes
We asked whether BMD and bone marker responses would be blunted in patients with fractures placed on teriparatide after fracture compared with patients without fractures on teriparatide.
Patients and Methods
We retrospectively collected data from 141 patients treated with teriparatide for osteoporosis. Seventy-seven patients received teriparatide after fractures (fracture group), whereas 64 were treated for other indications (nonfracture group). We determined BMD at the lumbar spine and at the proximal femur before and 12 and 24 months posttreatment. Bone markers (urine N-telopeptide [urine NTX], bone-specific alkaline phosphatase [BALP]) were measured at baseline and 3, 12, and 24 months posttreatment.
Results
Mean lumbar spine and hip BMDs at last followup increased from baseline with no differences between groups to approximately 9% and 4% at 24 months, respectively. Both bone markers increased from baseline in the nonfracture group, peaking at 12 months. For the fracture group, only urine NTX increased at 3 and 12 months posttreatment. Although the peak levels of both bone markers in the nonfracture group were greater, there was no difference between the two groups.
Conclusions
Fracture does not have a negative effect on the BMD and bone marker responses to teriparatide treatment. Clinicians should anticipate comparable BMD responses when treating patients with teriparatide for osteoporotic fractures and for other indications.
Level of Evidence
Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-011-2029-1
PMCID: PMC3270178  PMID: 21863393
16.  Bone fragility and imaging techniques 
Bone fragility is a silent condition that increases bone fracture risk, enhanced by low bone mass and microarchitecture deterioration of bone tissue that lead to osteoporosis. Fragility fractures are the major clinical manifestation of osteoporosis.
A large body of epidemiological data indicates that the current standard for predicting fragility fracture risk is an areal BMD (aBMD) measurement by DXA. Although mineral density measurements assess the quantity of bone, the quality of the tissue is an important predictor of fragility. Thus, bone strength is explained not only by BMD but also by macrostructural and microstructural characteristics of bone tissue. Imaging diagnostics, through the use of X-rays, DXA, Ultrasonography, CT and MR, provides methods for diagnosis and characterization of fractures, and semi- and quantitative methods for assessment of bone consistency and strength, that become precious for bone fragility clinical management if they are integrated by clinical risk factors. The last employment of sophisticated non-invasively imaging techniques in clinical research as high-resolution CT (hrCT), microCT (μ-CT), high-resolution MR (hrMR) and, microRM (μRM), combined with finite element analysis methods, open to new challenges in a better bone strength assessment to enhance the comprehension of biomechanical parameters and the prediction of fragility fractures.
PMCID: PMC2811356  PMID: 22461252
bone fragility, bone architecture, bone assessment, quantitative densitometry, high resolution imaging.
17.  Fractures of the distal humerus in elderly patients treated with a ring fixator 
International Orthopaedics  2010;35(1):101-106.
The aim of distal humerus fracture treatment is articular surface reduction and stable fixation for early mobilisation and rehabilitation. This is usually performed by open reduction and internal fixation with plates. In the elderly osteoporotic patient this treatment is difficult to achieve due to fixation failure in fragile bone. We present our experience with treatment by closed reduction and external fixation with a non-bridging ring fixator in distal humerus fractures in elderly patients. There were ten females, aged 70–89 (average 78.4). Fracture types (AO/ASIF) included three supracondylar fractures (type A) and seven intercondylar fractures (type C). All patients were treated by closed reduction and external fixation with a non-bridging ring fixator of the distal humerus and immediate postoperative mobilisation of the elbow. External fixation was removed on an average of 72 days (range 62–90). All fractures united. Average time to union was 56 days. Average range of movement at six months was 22° extension lag (range 15°–30°) and 115° flexion (range 110°–120°). Complications included one patient with transient radial palsy and one patient with a superficial decubitus ulcer on the chest wall from the hardware. Minimally invasive treatment by closed reduction and external fixation with a ring fixator is effective for treatment of fractures of the distal humerus in elderly patients with osteoporotic bone. This treatment enables immediate mobilisation of the elbow, and allows return to function. It should be considered an alternative to open reduction and internal fixation or total elbow replacement.
doi:10.1007/s00264-009-0938-3
PMCID: PMC3014495  PMID: 20135123
18.  Strontium ranelate in postmenopausal osteoporosis treatment: a critical appraisal 
Osteoporosis is a progressive and debilitating disease characterized by a massive bone loss with a deterioration of bone tissues, and a propensity for a fragility fracture. Strontium ranelate is the first antiosteoporotic treatment that has dual mode of action and simultaneously increases bone formation, while decreasing bone resorption, thus rebalancing bone turnover formation. Strontium ranelate rebalances bone turnover in favor of improved bone geometry, cortical thickness, trabecular bone morphology and intrinsic bone tissue quality, which translates into enhanced bone strength. This review describes the mechanism of the strontium ranelate action and its effects on bone mineral density, bone turnover, and osteoporotic fractures. The efficacy of strontium ranelate in postmenopausal osteoporosis treatment to reduce the risk of vertebral and hip fractures has been highlighted in several randomized, controlled trials. Treatment efficacy with strontium ranelate has been documented across a wide range of patient profiles: age, number of prevalent vertebral fractures, body mass index, and a family history of osteoporosis. Because strontium ranelate has a large spectrum of efficacy, it can be used to treat different subgroups of patients with postmenopausal osteoporosis. Strontium ranelate was shown to be relatively well tolerated and the safety aspects were good. Strontium ranelate should be considered as a first-line treatment for postmenopausal osteoporotic patients.
PMCID: PMC2971725  PMID: 21072291
osteoporosis; strontium ranelate; therapy
19.  Diagnostic challenges in osteoporosis. Indications for bone densitometry and establishing secondary causes. 
Canadian Family Physician  2001;47:1244-1250.
OBJECTIVE: To review indications for assessing bone mineral density (BMD) and to review patient characteristics and diseases associated with osteoporosis. QUALITY OF EVIDENCE: This paper is based on data from longitudinal observational studies of how BMD and other risk factors affect development of fragility fractures and on several peer-reviewed publications describing pathophysiology of bone turnover and pathogenesis of osteoporosis. Indications for obtaining BMD and monitoring treatment are based on the recommendations of the Osteoporosis Society of Canada derived from the consensus opinion of a panel of experts in osteoporosis and based on their review of the primary literature. MAIN MESSAGE: Measurement of BMD provides the best single objective predictor of the relative risk of fracture at sites such as the vertebrae, hip, and wrist, predicting the likelihood of fracture with as much accuracy as measurement of elevated blood pressure predicts stroke. In addition to making the diagnosis of osteoporosis, BMD measurements are used to monitor progression of osteoporosis and effects of therapy. At this date, dual energy x-ray absorptiometry is preferred for measuring BMD. The most likely causes of osteoporosis in any patient are age, hormone withdrawal (in both men and women), and drugs (particularly corticosteroids). Secondary causes, particularly hyperparathyroidism and multiple myeloma, should be excluded by performing appropriate laboratory tests. CONCLUSION: A BMD measurement should be obtained for patients at high risk of osteoporosis and fragility fractures to guide initiation and monitor success of therapy.
PMCID: PMC2018508  PMID: 11421053
20.  A systematic review of the effectiveness of interventions to improve post-fracture investigation and management of patients at risk of osteoporosis 
Background
There is a large quality of care gap for patients with osteoporosis. As a fragility fracture is a strong indicator of underlying osteoporosis, it offers an ideal opportunity to initiate investigation and treatment. However, studies of post-fracture populations document screening and treatment rates below 20% in most settings. This is despite the fact that bone mineral density (BMD) scans are effective at identifying patients at high risk of fracture, and effective drug treatments are widely available. Effective interventions are required to remedy this incongruity in current practice.
Methods
This study reviewed randomised controlled trials (RCT) involving fully qualified healthcare professionals caring for patients with a fragility fracture in all healthcare settings. Any intervention designed to modify the behaviour of healthcare professionals or implement a service delivery change was considered. The main outcomes were BMD scanning and osteoporosis treatment with anti-resorptive therapy. The electronic databases Medline and Embase were searched from 1994 to June 2010 to identify relevant articles in English. Post-intervention risk differences (RDs) were calculated for the main outcomes and any additional study primary outcomes; the trials were meta-analysed.
Results
A total of 2814 potentially relevant articles were sifted; 18 were assessed in full text. Nine RCTs evaluating ten interventions met the inclusion criteria for the review. All were from North America. Four studies focused on patients with a hip fracture, three on fractures of the wrist/distal forearm, and two included several fracture sites consistent with a fragility fracture. All studies reported positive effects of the intervention for the main study outcomes of BMD scanning and osteoporosis treatment. For BMD scanning the overall risk ratio (95% CI) was 2.8 (2.16 to 3.64); the RD was 36% (21% to 50%). For treatment with anti-resorptive therapy the overall risk ratio (95% CI) was 2.48 (1.92 to 3.2); the RD was 20% (10% to 30%).
Conclusions
All interventions produced positive effects on BMD scanning and osteoporosis treatment rates post-fracture. Despite sizeable increases, investigation and treatment rates remain sub-optimal. Long-term compliance with osteoporosis medications needs to be addressed, as the majority of studies reported treatment rates at six-month follow up only. Studies would be more informative if treatment criteria were defined a priori to facilitate understanding of whether patients were being treated appropriately and integrated economic analyses would be helpful for informing policy implementation decisions.
doi:10.1186/1748-5908-5-80
PMCID: PMC2988064  PMID: 20969769
21.  Pharmacological agents and bone healing 
Osteoporosis is the most common alteration of bone metabolism. It derives from an increase in bone resorption with respect to bone formation and is characterized by microarchitectural alterations, decreased bone mass and increased risk of fracture. The coupling between bone formation and resorption is a fundamental concept in skeletal metabolism, and it explains how a certain amount of removed tissue can be replaced by the same amount of new bone. Various substances used to treat osteoporosis may also be used for orthopaedic conditions such as fracture healing, implant fixation, bone grafts and osteonecrosis. Fracture healing consists in the replacement of the lost bone by a tissue that has the same biomechanical properties as those preceding the fracture. The repair process is triggered by the local response to the tissue injury that damaged the continuity of bone. The duration of each phase of the healing process can vary significantly, depending on the site and characteristics of the fracture, on patient related factors and on the treatment choice. While most of the fractures heal with conventional treatment, they can also cause permanent damage and complications, especially in a certain kind of patients. Osteoporosis and old age may contribute in delaying or impairing the reparative process. In animal models the healing process is slower in older and/or ovariectomized animals. Biomechanical tests have also shown that bone strength is compromised in human osteoporotic cadaver bone. The same problems were highlighted in the surgical treatment of fractures in osteoporotic patients. Mainly in the treatment of hip fractures there is an increased risk of cut-out, re-fractures and implant failure in patients with osteoporosis. Preclinical studies have shown that certain pharmacological agents (bisphosphonates, strontium ranelate, teriparatide) may enhance osseointegration and stimulate reparative processes. They may be administered systemically and/or used locally at the fracture site on the implant surface. The aim of fracture treatment is to restore bone biomechanical properties and to allow restoring normal function at the affected site. If the new pharmacological approaches could be translated into clinical benefit and offered to patients with osteoporosis or other factors that put at risk the process of healing (subjects with severe loss of substance or fractures at high risk of complications), they could represent a valuable aid in the treatment of fractures.
PMCID: PMC2781222  PMID: 22461164
fracture healing, bone remodeling, osteoporosis treatment.
22.  Osteoporosis in celiac disease and in endocrine and reproductive disorders 
As the increase in lifespan brings to light diseases that were previously not clinically detectable, osteoporosis has become an issue of worldwide significance. The disease is marked by a loss of bone mass; the bones become less dense, fragile and more prone to fracturing. Because it is regulated by endocrine and environmental factors, osteoporosis presents a multifactorial etiopathogenesis, with the genetic component accounting for 70% of an individual variation in bone mass density (BMD), the principal determinant, with age, of fracture risk. Pathological conditions such as celiac disease (CD) exacerbate the process of bone loss, so that the occurrence of osteoporosis in celiac subjects is of particular note: indeed, the screening of osteoporosis patients for this disease is advisable, since it may be the only sign of undiagnosed CD. An increase in interleukin IL-1β, of the IL-1 system, in the relatives of celiac patients confirms the genetic predisposition to osteoporosis and its presence is evidence of an association between the two conditions. The direct effect on the bones of CD is secondary to poor absorption of calcium and vitamin D. In women osteoporosis is indirectly associated with early menopause and amenorrhea, and it may follow prolonged breast-feeding and frequent pregnancies, while in men it is associated with hypogonadism and GH deficit. These endocrine and non-endocrine factors exert their effects on bones by modulating the RANK/RANK-L/OPG system. An appropriate lifestyle from adolescence onwards, together with early diagnosis of and treatment for CD and primary and secondary endocrine pathologies are important for the prevention of damage to the bones.
doi:10.3748/wjg.14.498
PMCID: PMC2681138  PMID: 18203279
Osteoporosis; Celiac disease; Menopause; Estrogens; Hypogonadism; Micronutrients
23.  Accelerated tibial fracture union in the third trimester of pregnancy: a case report 
Introduction
We present a case of accelerated tibial fracture union in the third trimester of pregnancy. This is of particular relevance to orthopaedic surgeons, who must be made aware of the potentially accelerated healing response in pregnancy and the requirement for prompt treatment.
Case presentation
A 40 year old woman at 34 weeks gestational age sustained a displaced fracture of the tibial shaft. This was initially treated conservatively in plaster with view to intra-medullary nailing postpartum. Following an emergency caesarean section, the patient was able to fully weight bear without pain 4 weeks post injury, indicating clinical union. Radiographs demonstrated radiological union with good alignment and abundant callus formation. Fracture union occurred within 4 weeks, less than half the time expected for a conservatively treated tibial shaft fracture.
Conclusion
Long bone fractures in pregnancy require clear and precise management plans as fracture healing is potentially accelerated. Non-operative treatment is advisable provided satisfactory alignment of the fracture is achieved.
doi:10.1186/1752-1947-2-44
PMCID: PMC2265291  PMID: 18261239
24.  The Management of Osteoporosis among Home Health and Long Term Care Patients with a Prior Fracture 
Southern medical journal  2009;102(4):397-404.
Osteoporosis is a growing health concern as the number of senior adults continues to increase worldwide. Falls and fractures are very common among frail older adults requiring home health and long-term care. Preventative strategies for reducing falls have been identified and many therapies (both prescription and non-prescription) with proven efficacy for reducing fracture risk are available. However, many practitioners overlook the fact that a fragility fracture is diagnostic for osteoporosis even without knowledge of bone mineral density testing. As a result, osteoporosis is infrequently diagnosed and treated in the elderly after a fracture. Based on existing literature, we have developed an algorithm for the assessment and treatment of osteoporosis among persons with known prior fracture(s) living in long-term care facilities or receiving home health care.
doi:10.1097/SMJ.0b013e31819bc1d3
PMCID: PMC2720154  PMID: 19279529
25.  Emerging Therapies to Prevent Skeletal Morbidity in Men With Prostate Cancer 
Journal of Clinical Oncology  2011;29(27):3705-3714.
Skeletal morbidity is a prominent burden to men with advanced prostate cancer throughout the natural history of the disease. Bone metastases can cause pain and greatly elevate the risk for fractures and other structural complications. Distinct from the problem of metastases, treatment-related osteoporosis and associated fragility fractures are potential complications of androgen-deprivation therapy. Bone-targeted therapies for prostate cancer have therefore been the focus of considerable research and drug development efforts. The osteoclast is a validated therapeutic target in the management of prostate cancer. Osteoclast inhibition with zoledronic acid (a bisphosphonate) or with denosumab (a monoclonal antibody to RANK ligand) reduces risk for skeletal events in men with castration-resistant prostate cancer metastatic to bone. Osteoclast inhibition with any of several bisphosphonates improves bone mineral density, a surrogate for osteoporotic fracture risk. Denosumab and toremifene (a selective estrogen receptor modulator) have each been shown to reduce osteoporotic fracture risk among men receiving androgen-deprivation therapy. Beta-emitting radiopharmaceuticals reduce pain due to metastatic disease. Investigations involving alpha-emitting radium-223, endothelin-A receptor antagonists atrasentan and zibotentan, proto-oncogene tyrosine-protein kinase (SRC) inhibitor dasatinib, and tyrosine kinase inhibitor cabozantinib (XL184) are ongoing in clinical trials and are also discussed.
doi:10.1200/JCO.2010.34.4994
PMCID: PMC3675709  PMID: 21860001

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