The August 2024 Spine Roundup. 360. looks at: Laminectomy adjacent to instrumented fusion increases adjacent segment disease; Influence of the timing of surgery for cervical spinal cord injury without bone injury in the elderly: a retrospective multicentre study; Lumbar vertebral body tethering: single-centre outcomes and reoperations in a consecutive series of 106 patients; Machine-learning algorithms for predicting Cobb angle beyond 25° in female adolescent idiopathic scoliosis patients; Pain in adolescent idiopathic scoliosis;
Aims. A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 10. 6. cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. Results. Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores – RUST and Allen score – histologically compared to controls. Conclusion. We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose
The December 2015 Spine Roundup360 looks at: Ketamine in scoliosis surgery;
An 81-year-old woman presented with a fracture
in the left femur. She had well-fixed bilateral hip replacements
and had received long-term bisphosphonate treatment. Prolonged bisphosphonate
use has been recently linked with atypical subtrochanteric and diaphyseal
femoral fractures. While the current definition of an atypical fracture
of the femur excludes peri-prosthetic fractures, this case suggests
that they do occur and should be considered in patients with severe
osteopenia. Union of the fracture followed cessation of bisphosphonates
and treatment with
Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis. This single-centre retrospective study included 398 hip joints of patients who underwent THA. Using medical records, we examined preoperative bone mineral density measures of the hip and lumbar spine using dual energy X-ray absorptiometry (DXA) scans and the medications used to treat osteoporosis at the time of admission. We also assessed the following osteoporosis-related biomarkers: tartrate-resistant acid phosphatase 5b (TRACP-5b); total procollagen type 1 amino-terminal propeptide (total P1NP); intact parathyroid hormone; and homocysteine.Aims
Methods
Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP. Using quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined. Western blotting was used to examine the expression of PAK2 protein. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. To examine the osteogenic differentiation, Alizarin red along with ALP staining was used. RNA immunoprecipitation assay and bioinformatics analysis, as well as a dual-luciferase reporter, were used to study the association between PCBP1-AS1, PAK2, and miR-126-5p.Aims
Methods
Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis. The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Aims
Methods
Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model. Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies.Aims
Methods
The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip. We retrospectively reviewed standing whole-leg radiographs from patients who underwent knee arthroplasties from 2012 to 2020 at our institute. Patients with previous hip surgery, Kellgren–Lawrence grade ≥ II hip osteoarthritis, hip dysplasia, or rheumatoid arthritis were excluded. The rate of hip joint space narrowing was measured in 398 patients (796 hips), and the effects of the use of bisphosphonates were examined using the multivariate regression model and the propensity score matching (1:2) model.Aims
Methods
Postoperative complication rates remain relatively high after adult spinal deformity (ASD) surgery. The extent to which modifiable patient-related factors influence complication rates in patients with ASD has not been effectively evaluated. The aim of this retrospective cohort study was to evaluate the association between modifiable patient-related factors and complications after corrective surgery for ASD. ASD patients with two-year data were included. Complications were categorized as follows: any complication, major, medical, surgical, major mechanical, major radiological, and reoperation. Modifiable risk factors included smoking, obesity, osteoporosis, alcohol use, depression, psychiatric diagnosis, and hypertension. Patients were stratified by the degree of baseline deformity (low degree of deformity (LowDef)/high degree of deformity (HighDef): below or above 20°) and age (Older/Younger: above or below 65 years). Complication rates were compared for modifiable risk factors in each age/deformity group, using multivariable logistic regression analysis to adjust for confounders.Aims
Methods
The aims of this study were to characterize the incidence and risk factors associated with stress fractures following periacetabular osteotomy, and to determine their effect on osteotomy union. We retrospectively reviewed all periacetabular osteotomies (PAOs) performed for developmental dysplasia of the hip (DDH) at one institution over a six-year period between 2012 and 2017. Perioperative factors were recorded, and included demographic and surgical data. Postoperatively, patients were followed for a minimum of one year with anteroposterior and false profile radiographs of the pelvis to monitor for evidence of stress fracture and union of osteotomies. We characterized the incidence and locations of stress fractures, and used univariate and multivariable analysis to identify factors predictive of stress fracture and the association of stress fracture on osteotomy union.Aims
Methods
The aim of this study was to investigate the outcome of periprosthetic fractures of the humerus and to assess the uniformity of the classifications used for these fractures (including those around elbow and/or shoulder arthroplasties) by performing a systematic review of the literature. A systematic search was conducted using the National Institute for Health and Care Excellence Healthcare Databases Advance Search. For inclusion, studies had to report clinical outcomes following the management of periprosthetic fractures of the humerus. The protocol was registered on the PROSPERO database.Aims
Methods
The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD). A total of 54 human cadaver forearms (ten singles, 22 pairs) (19 to 90 years) were systematically assessed by clinical radiograph (XR), dual-energy X-ray absorptiometry (DXA), CT, as well as high-resolution peripheral quantitative CT (HR-pQCT). Cortical bone thickness (CBT) of the distal radius was measured on XR and CT scans, and two cortical indices mean average (CBTavg) and gauge (CBTg) were determined. These cortical indices were compared to the BMD of the distal radius determined by DXA (areal BMD (aBMD)) and HR-pQCT (volumetric BMD (vBMD)). Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC) were used to compare the results and degree of reliability.Aims
Methods
Bone health assessment and the prescription of medication for secondary fracture prevention have become an integral part of the acute management of patients with hip fracture. However, there is little evidence regarding compliance with prescription guidelines and subsequent adherence to medication in this patient group. The World Hip Trauma Evaluation (WHiTE) is a multicentre, prospective cohort of hip fracture patients in NHS hospitals in England and Wales. Patients aged 60 years and older who received operative treatment for a hip fracture were eligible for inclusion in WHiTE. The prescription of bone protection medications was recorded from participants’ discharge summaries, and participant-reported use of bone protection medications was recorded at 120 days following surgery.Aims
Patients and Methods
Currently, periprosthetic fractures are excluded from the American Society for Bone and Mineral Research (ASBMR) definition of atypical femoral fracture (AFFs). This study aims to report on a series of periprosthetic femoral fractures (PFFs) that otherwise meet the criteria for AFFs. Secondary aims were to identify predictors of periprosthetic atypical femoral fractures (PAFFs) and quantify the complications of treatment. This was a retrospective case control study of consecutive patients with periprosthetic femoral fractures between 2007 and 2017. Two observers identified 16 PAFF cases (mean age 73.9 years (44 to 88), 14 female patients) and 17 typical periprosthetic fractures in patients on bisphosphonate therapy as controls (mean age 80.7 years (60 to 86, 13 female patients). Univariate and multivariate analysis was performed to identify predictors of PAFF. Management and complications were recorded.Aims
Patients and Methods
Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.
Bisphosphonates are widely used as first-line treatment for primary and secondary prevention of fragility fractures. Whilst they have proved effective in this role, there is growing concern over their long-term use, with much evidence linking bisphosphonate-related suppression of bone remodelling to an increased risk of atypical subtrochanteric fractures of the femur (AFFs). The objective of this article is to review this evidence, while presenting the current available strategies for the management of AFFs. We present an evaluation of current literature relating to the pathogenesis and treatment of AFFs in the context of bisphosphonate use.Objectives
Methods
Treatment guidelines for atypical femoral fractures associated
with bisphosphonates have not been established. We conducted a systematic
review of the treatment of atypical femoral fractures first, to
evaluate the outcomes of surgical fixation of complete atypical fractures
and secondly, to assess whether prophylactic surgery is necessary
for incomplete atypical fractures. Case reports and series were identified from the PubMed database
and were included if they described the treatment of atypical femoral
fractures. In total, 77 publications met our inclusion criteria
and 733 patients with 834 atypical complete or incomplete femoral fractures
were identified.Aims
Materials and Methods
The aim of this study was to evaluate the outcomes of a salvage procedure using a 95° angled blade plate for failed osteosynthesis of atypical subtrochanteric femoral fractures associated with the long-term use of bisphosphonates. These were compared with those for failed osteosynthesis of subtrochanteric fractures not associated with bisphosphonate treatment. Between October 2008 and July 2016, 14 patients with failed osteosynthesis of an atypical subtrochanteric femoral fracture were treated with a blade plate (atypical group). Their mean age was 67.8 years (60 to 74); all were female. During the same period, 21 patients with failed osteosynthesis of a typical subtrochanteric fracture underwent restabilization using a blade plate (typical group). Outcome variables included the time of union, postoperative complications, Harris Hip Score, and Sanders functional rating scale.Aims
Patients and Methods
For over a decade, bisphosphonate administration
has evolved and become the cornerstone of the prevention and treatment
of fragility fractures. Millions of post-menopausal women have relied
on, and continue to depend on, the long-acting, bone density-maintaining
pharmaceutical drug to prevent low-energy fractures. In return,
we have seen the number of fragility fractures decrease, along with
associated costs and emotional benefits. However, with any drug,
there are often concerns with side effects and complications, and
this unique drug class is seeing one such complication in atypical
subtrochanteric femoral fracture, counterproductive to that which
it was designed to prevent. This has created concern over long-term
bisphosphonate administration and its potential link to these atypical
fractures. There is controversial evidence surrounding such a definitive
link, and no protocol for managing these fractures. This review offers the latest information regarding this rare
but increasingly controversial adverse effect and its potential
connection to one of the most successful forms of treatment that
is available for the management of fragility fractures.
Although vertebroplasty is very effective for relieving acute pain from an osteoporotic vertebral compression fracture, not all patients who undergo vertebroplasty receive the same degree of benefit from the procedure. In order to identify the ideal candidate for vertebroplasty, pre-operative prognostic demographic or clinico-radiological factors need to be identified. The objective of this study was to identify the pre-operative prognostic factors related to the effect of vertebroplasty on acute pain control using a cohort of surgically and non-surgically managed patients. Patients with single-level acute osteoporotic vertebral compression fracture at thoracolumbar junction (T10 to L2) were followed. If the patients were not satisfied with acute pain reduction after a three-week conservative treatment, vertebroplasty was recommended. Pain assessment was carried out at the time of diagnosis, as well as three, four, six, and 12 weeks after the diagnosis. The effect of vertebroplasty, compared with conservative treatment, on back pain (visual analogue score, VAS) was analysed with the use of analysis-of-covariance models that adjusted for pre-operative VAS scores.Objectives
Patients and Methods
The ageing population and an increase in both
the incidence and prevalence of cancer pose a healthcare challenge, some
of which is borne by the orthopaedic community in the form of osteoporotic
fractures and metastatic bone disease. In recent years there has
been an increasing understanding of the pathways involved in bone
metabolism relevant to osteoporosis and metastases in bone. Newer
therapies may aid the management of these problems. One group of
drugs, the antibody mediated anti-resorptive therapies (AMARTs)
use antibodies to block bone resorption pathways. This review seeks
to present a synopsis of the guidelines, pharmacology and potential pathophysiology
of AMARTs and other new anti-resorptive drugs. We evaluate the literature relating to AMARTs and new anti-resorptives
with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for
Nuclear Factor Kappa-B Ligand. It is the first AMART approved by
the National Institute for Health and Clinical Excellence and the
US Food and Drug Administration. Other novel anti-resorptives awaiting
approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and
prevention of the complications of bone metastases. Recent evidence
suggests, however, that denosumab may have an adverse event profile
similar to bisphosphonates, including atypical femoral fractures.
It is, therefore, essential that orthopaedic surgeons are conversant
with these medications and their safe usage. Take home message: Denosumab has important orthopaedic indications
and has been shown to significantly reduce patient morbidity in
osteoporosis and metastatic bone disease. Cite this article:
An atypical femoral fracture (AFF), with a transverse
fracture radiologically through the lateral cortex is a rare but serious
condition. In order to improve our ability to identify patients
with this condition, we retrospectively surveyed all subtrochanteric,
peri-implant and diaphyseal femoral fractures in patients aged ≥ 65
years who underwent surgical treatment at our hospital between 2004
and 2011. We describe the incidence of atypical fractures and their characteristics,
with observational data including a review of the hospital and general
practitioner records. Clinical outcomes were evaluated using the
Harris hip score (HHS) and the timed up-and-go (TUG) test. Atypical fractures only occurred in women with an incidence of
9.8 per 100 000 person-years. The incidence in those who were treated
with bisphosphonates was 79.0 per 100 000 person-years; eight of
17 fractures occurred around metal implants. There was a high incidence
of delayed union and revision surgery. A total of nine patients (ten
AFFs) were available for review at a mean follow-up of 36.5 months
(10 to 104). The clinical outcome was poor with a mean HHS of 58.9
(95% CI 47.4 to 70.4) and a mean TUG test of 25.7 s (95% CI 12.7
to 38.8). The delay in diagnosis and treatment of AFF may result from a
lack of knowledge of this condition. Cite this article:
Management of bisphosphonate-associated subtrochanteric
fractures remains opinion- or consensus-based. There are limited
data regarding the outcomes of this fracture. We retrospectively reviewed 33 consecutive female patients with
a mean age of 67.5 years (47 to 91) who were treated surgically
between May 2004 and October 2009. The mean follow-up was 21.7 months
(0 to 53). Medical records and radiographs were reviewed to determine
the post-operative ambulatory status, time to clinical and radiological
union and post-fixation complications such as implant failure and
need for second surgery. The predominant fixation method was with an extramedullary device
in 23 patients. 25 (75%) patients were placed on wheelchair mobilisation
or no weight-bearing initially. The mean time to full weight-bearing
was 7.1 months (2.2 to 29.7). The mean time for fracture site pain
to cease was 6.2 months (1.2 to 17.1). The mean time to radiological
union was 10.0 months (2.2 to 27.5). Implant failure was seen in
seven patients (23%, 95 confidence interval (CI) 11.8 to 40.9).
Revision surgery was required in ten patients (33%, 95 CI 19.2 to
51.2). A large proportion of the patients required revision surgery
and suffered implant failure. This fracture is associated with slow
healing and prolonged post-operative immobility. Cite this article:
Osteoporotic vertebral compression fractures
(VCFs) are an increasing public health problem. Recently, randomised
controlled trials on the use of kyphoplasty and vertebroplasty in
the treatment of these fractures have been published, but no definitive conclusions
have been reached on the role of these interventions. The major
problem encountered when trying to perform a meta-analysis of the
available studies for the use of cementoplasty in patients with
a VCF is that conservative management has not been standardised.
Forms of conservative treatment commonly used in these patients
include bed rest, analgesic medication, physiotherapy and bracing. In this review, we report the best evidence available on the
conservative care of patients with osteoporotic VCFs and associated
back pain, focusing on the role of the most commonly used spinal
orthoses. Although orthoses are used for the management of these patients,
to date, there has been only one randomised controlled trial published
evaluating their value. Until the best conservative management for
patients with VCFs is defined and standardised, no conclusions can
be drawn on the superiority or otherwise of cementoplasty techniques
over conservative management.
Osteoporosis and fragility fractures in men constitute a considerable burden in healthcare. We have reviewed 2035 men aged over 50 years with 2142 fractures to clarify the epidemiology of these injuries and their underlying risk factors. The prevalence of osteoporosis ranged between 17.5% in fractures of the ankle and 57.8% in those of the hip. The main risk factors associated with osteoporosis were smoking (47.4%), alcohol excess (36.2%), body mass index <
21 (12.8%) and a family history of osteoporosis (8.4%). Immobility, smoking, self-reported alcohol excess, a low body mass index, age ≥72 and loss in height were significantly more common among men with fractures of the hip than in those with fractures elsewhere.
