Treatment Of Vertebral Osteoporosis Research Articles

[Translated article] Evaluation, differential diagnosis and treatment of vertebral osteoporosis: How to avoid the occurrence of new fractures

Osteoporosis is a highly prevalent and multifactorial disease whose main manifestation is the appearance of fragility or low-impact fractures. The most frequent locations of osteoporotic fractures occur at the vertebrae, femoral, distal end of the radius and humerus. Osteoporotic vertebral fracture deserves special mention among them due to its prevalence, importance as it often goes unnoticed and medium-long term consequences are: pain, deformity, disability and deterioration in quality of life. In this review we will focus on the classification and initial evaluation of the patient with osteoporosis, estimation of risk factors, laboratory and imaging studies for an adequate assessment using simple radiography, dual densitometry and magnetic resonance imaging. We will also address the main aspects of the differential diagnosis, treatment and prevention of vertebral fragility fracture, briefly reviewing the main therapeutic agents currently used for its prevention and treatment.

Does Zoledronic Acid Provide a Good Clinical Outcome in Patients With Chronic Back Pain Associated With Vertebral Osteoporosis?

Background Osteoporosis is a chronic, progressive, systemic condition of the skeletal tissue that is characterized by reduced bone density, microarchitecture deterioration, and fragile bones, making osteoporotic fractures or fragility fractures more likely to occur. This condition often remains asymptomatic and undiagnosed until it presents with fragility fractures. The condition is associated with a significant socioeconomic burden with disability, morbidity, and mortality. Therefore, early diagnosis, as well as treatment, is needed to prevent fractures. Intravenous zoledronic is an effective bisphosphonate with high patient compliance due to once-yearly dosing. The present study aims to determine whether zoledronic acid effectively treats chronic back pain in people with osteoporosis. Materials and methods Seventy patients above the age of 60 years presented with complaints of chronic low back aches to the outpatient department of orthopedics, R L Jalappa Hospital & Research Centre attached to Sri Devaraj Urs Medical College. The study was conducted between November 2016 and November 2018. Results All the patients found excellent clinical improvement following zoledronic acid infusion in early and long-term follow-ups. Additionally, it was found that zoledronic acid's effectiveness was excellent, with significant improvement in bone mineral density (BMD), T-score, and Z-score. Conclusion Early diagnosis and treatment of vertebral osteoporosis is the most important factor in preventing fragility fractures. Zoledronic acid, an antiresorptive drug with better compliance, is very effective in controlling low back pain, improving bone mineral density, and preventing the occurrence of atraumatic fragility fractures. With all the above factors, zoledronic acid is a preferable bisphosphonate for the treatment and prevention of osteoporosis compared to other modalities of treatment of osteoporosis.

Diagnostics and surgical treatment of vertebral osteoporosis

The retrospective analysis of clinical and radiological diagnostics of 76 patients with vertebral osteoporosis among which women prevailed (82.9%) is carried out. The average age was 57,7 ± 5,3 years. The complex diagnostics consists of the survey x-ray,the x-ray absorptiometry, the quantitative computed tomography, spiral computed tomography and magnetic resonance imaging procedure. The quantitative computed tomography is characterized by the highest diagnostic information value (sensitivity - 99.4%, specificity - 99.5% and the accuracy - 99.3%). Surgical treatment consisted in rigid (7.9%) and dynamic (10.5%) vertebral fixation and puncture vertebroplasty (81.6%), which was consist in a dereception of underlying facet joints with introduction into it the solution consisting in equal quantities of local anesthetic and alcohol 70° (1.5-2.0 ml). The optimized technique of vertebroplasty with an additional dereception of facet joints allows to increase the level of social rehabilitation of patients by 10.2% with full regress of a pain syndrome.

Raloxifene for older women: a review of the literature.

Raloxifene is a non-steroidal selective estrogen-receptor modulator (SERM) which is used for prevention and treatment of postmenopausal osteoporosis. Raloxifene decreases the incidence of vertebral fractures by 30%-50% in postmenopausal women with osteoporosis but has not been shown to decrease the incidence of hip fractures or other non-vertebral fractures. At the present time, estrogen-replacement therapy and bisphosphonate treatment are the only medical treatments that are proven to prevent hip fractures with the exception of vitamin D and calcium replacement, which has been shown to prevent hip fractures in elderly individuals and nursing home residents. Raloxifene has been shown to have additive effects on bone turnover and bone mineral density (BMD) when used along with alendronate and teriparatide. Raloxifene could have a role in renal failure as it has been shown to increase BMD of the vertebra over 1 year of therapy. Raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer. The increased incidence of venous thromboembolism is the main concern of raloxifene therapy and previous history of venous thromboembolism is a contraindication for use of raloxifene. Raloxifene has a role in treatment of vertebral osteoporosis in older women. The decision to use raloxifene should be based on evaluation of fracture risk and on potential other benefits than fracture reduction along with consideration of side effects.

Staged-Injection Procedure to Prevent Cement Leakage During Vertebroplasty

Fibrin sealant (FS) combined with or without growth factor was used to improve the micro-architectural and biomechanical properties of vertebral body in osteoporotic ovine spine. To analyze the treatment effects of bovine bone morphogenetic protein (bBMP) combined with FS on osteopenic ovine vertebral architecture, bone mineral density, and biomechanics in vivo. Vertebroplasty and kyphoplasty were used to treat spinal osteoporosis. They can increase strength of vertebrae physically. However, each has specific disadvantages. bBMP could rapidly increasing bone formation and suppressing bone resorption, but little is known about its effect on ovariectomized-induced osteoporosis. Six sheep underwent ovariectomy and were placed on a low-calcium diet. Twelve months later, according to Ladin square design, L4-L6 vertebrae in all sheep were randomly assigned to 3 treatment groups: A (30 mg bBMP/1.5 mL FS), B (30 mg bBMP) and C (1.5 mL FS). All materials were injected into the assigned vertebra transpedicularly. Animals were killed 3 months after injection, and bone mineral density (BMD), biomechanics, and histomorphometry were assessed. Analysis of variance was used to determine effects of bBMP/FS (alpha = 0.05). The BMD in Group 1 was 17.1% and 14.7% higher than that in Group 2 and Group 3, respectively. The micro-CT reconstruction analysis showed that the density and connectivity of trabecular bone in bBMP/FS treated vertebrae were higher than those in control groups. The mechanical properties (yield stress, ultimate stress, energy absorption, bone modulus) of the vertebrae were also significantly higher. In this study, local bBMP/FS treatment showed a positive trend in improving BMD, histomorphometric parameters, and mechanical strength of osteoporotic vertebra. Slow release of bBMP using FS appeared to be an effective method of protein delivery. The use of bBMP/FS in the treatment of vertebral osteoporosis in an attempt to enhance bone strength merits further study.

In vivo BMP-7 (OP-1) enhancement of osteoporotic vertebral bodies in an ovine model

Background context Prevention of osteoporotic vertebral fractures could help at-risk individuals avoid the pain and morbidity associated with these fractures. Currently, patients with osteoporosis are treated with systemic medications to reduce fracture risk. Although effective, these therapies do not eliminate fractures and also tend to have a gradual time-dependent effect on fracture risk. The mechanism of action of the bone morphogenetic protein (BMP) family theoretically makes these molecules candidates for rapidly enhancing local bone structure. Study design An in vivo study analyzing the effects of BMP-7 (osteogenic protein 1 [OP-1]) treatment on osteopenic ovine vertebral architecture and biomechanics. Purpose We tested the hypothesis that local injection of OP-1 into osteopenic ovine vertebrae will improve bone mass and trabecular distribution, thereby reducing bone fragility and fracture risk. We specifically evaluated compressive biomechanics and morphology of osteopenic ovine vertebral bodies 6 months after local OP-1 treatment. Study design In vivo animal study. Methods Skeletally mature sheep (n=24) underwent ovariectomy and were placed on low cation relative to anion diet. These interventions reduce bone density and induce skeletal fragility. After 6 months, sheep were randomly assigned to six treatment groups based on OP-1 dose (370 mg or 0 mg) and carrier with 4 animals/treatment group. Carriers A and B were poly- l-glycolic acid (PLGA) biospheres with different release kinetics (B allowing sustained BMP release); Carrier C was carboxymethylcellulose. After creating an 8-mm-diameter defect in the midvertebral body, sheep underwent intravertebral body implantation at two nonadjacent levels. Animals were euthanized 6 months after implantation and bone mineral density (BMD), biomechanics, and histomorphometry were assessed. Two-way analysis of variance was used to determine effects of OP-1 (α=0.05). Results An 81.9%, 333.2%, and 39.9% increase in stiffness was seen for OP-1 treated vertebra with Carriers A, B, and C respectively. Although these effects did not reach statistical significance, trends toward improvement were evident. Histology showed varied degrees of bony healing in the injection sites. Histomorphometrically, OP-1 treated vertebrae showed improvements in percent bone of up to 38% and star volume of up to 55% (with Carrier B). Improvements in whole vertebral body BMD were not detected for any treatment. Conclusion In this study, local OP-1 treatment showed a positive trend in improving mechanical strength and histomorphometric parameters of osteopenic vertebra, despite the absence of consistent change in BMD. Controlled slow release of OP-1 using PLGA microspheres appeared to be the most effective method of protein delivery. In conclusion, we feel that the pilot data suggest that the use of OP-1 in the treatment of vertebral osteoporosis in an attempt to enhance bone strength merits further study.

Fluoride pharmacokinetics and changes in lumbar spine and hip bone mineral density.

Debate about the use of fluoride for the treatment of vertebral osteoporosis has centered not only on whether fluoride treatment decreases vertebral fractures, but also the interindividual vertebral bone mineral density (BMD) response, the potential for nonvertebral fractures, as well as side effects and tolerability. These effects may be dose dependent and, in this study, we examine the pharmacokinetics of sodium monofluorophosphate (MFP) in osteoporotic patients and relate this to changes in BMD. Plasma fluoride absorption curves were measured from 0 to 6 h after ingestion of MFP at baseline and during long-term dosing in 21 patients with vertebral osteoporosis (T scores < or = 2). BMD was measured at baseline and at 12 months at the lumbar spine (LS), femoral neck (FN), trochanter, and Ward's triangle. We found that fluoride elimination was inversely related to creatinine clearance. LS BMD increased from a median of 0.77 g/cm2 (range 0.69 to 0.99) at baseline to 0.88 g/cm2 (0.75 to 1.13) (p < 0.001) after 12 months. This equates to a median increase of 12% (range -1.2 to 37). Median femoral neck BMD decreased from 0.75 g/cm2 (0.62 to 0.94) at baseline to 0.69 g/cm2 (0.62 to 0.92) (p = 0.13) after 12 months. This equates to a decrease of -2% (-19 to 10). BMD at the other hip sites also decreased slightly. Changes in LS and FN BMD were not significantly related (r = 0.28, p = 0.29). The various pharmacokinetic parameters measured were not related to changes in LS BMD; however, there was an inverse relationship between trough fluoride concentration during long-term dosing and change in FN BMD. Further studies are required to see if this relationship can be used to monitor osteoporotic patients treated with fluoride and prevent significant decreases in FN BMD and possibly fractures at this site.

Human parathyroid peptide treatment of vertebral osteoporosis.

Previous studies have shown that treatment with daily injections of human parathyroid peptide (hPTH) 1-34 increase axial cancellous bone mass partially at the expense of peripheral cortical bone. In the present work the same hPTH 1-34 regime given for 12 months has been combined with oestrogen or nandrolone therapy to control peripheral bone resorption. Spinal and iliac cancellous (but not cortical) bone increased by 40%-50% above initial values while no perceptible changes occurred in radial cortical or cancellous bone. The evidence of radiokinetic and histomorphometric studies performed before and in the last months of treatment suggested that bone remodeling had proceeded through a transient anabolic phase with increased activation, but that activation had become normal after 11-12 months in the cancellous bone of the ilium whereas it continued to be raised elsewhere in the skeleton. It is concluded that in combination with oestrogens, hPTH peptides given daily injections hold great promise for the treatment of patients with osteoporosis who have already lost substantial amounts of spinal cancellous bone.

Side-effects of fluoride therapy

Fluoride stimulates bone formation and is used in the treatment of vertebral osteoporosis. Epidemiological and experimental studies have shown that fluoride bone is denser but not always stronger than normal bone, and the main side-effects attributed to this drug involve bone tissue. True fractures, with cortical rupture, are few (near 5%); their rate seems to correspond to that generally found in osteoporotic patients without treatment. On the other hand, stress fractures and arthralgia of the lower limbs are much more frequent (near 30%), but they often follow a benign course. Digestive tolerance of fluoride is now good, improved by the introduction of gastro-resistant industrial galenicals. However, the question of whether the risk/benefit ratio is positive is always under discussion.