Introduction. We report a case which total knee arthroplasty (TKA) was able to be performed on schedule for the patient with occult fracture of proximal tibia which seemed to have occurred three months prior to the surgery, and has healed in short period of time by the use of Teriparatide. Case report. The patient is 84-year-old female, having right knee pain for past 7 years. Her knee pain increased by passive extension maneuver that was done by a bonesetter 3 months prior to the surgery. On her initial visit, the X-ray finding was severe medial osteoarthritis, and femorotibial angle (FTA) in the upright film was 197°, but there was no other disorder including fracture. Since the bone mineral density (BMD) of affected femoral neck was 62%YAM, and affected lateral femoral condyle as well as lateral tibial condyle seemed very porotic, we started using daily 20μg Teriparatide injection from 3 months prior to the surgery. Proximal tibial fracture was presented in the X-ray taken on the day before surgery, but since adequate bone union has already been formed, surgery was performed on schedule. Tibial implant with long stem was used for just to be certain. Thanks to the Teriparatide, the condition of cancellous bone in cut surface was excellent, and reaming of the tibia through fracture area felt very solid. Discussion. Proximal tibial fracture that occurred just before TKA is very rare. The fracture in this case was probably due to the maneuver done by the bonesetter. Teriparatide is indicated when osteoporosis is severe and the patient is at risk for fracture. We also indicate Teriparatide for the patients whose femoral neck BMD is very low and severe valgus knee or varus knee is present. Unloaded side of femoral or tibial condyle is usually very porotic in such a case. In our case, the fracture was so called fragility fracture which was found incidentally the day before surgery, but TKA could be done on schedule since adequate callus has been formed by the use of Teriparatide which started 3 months prior to the surgery

Most of researches related to osteoporosis emphasized on trabecular bone loss. However, cortical bone has a prominent role on bone strength determined by bone quality, such as 2D or 3D geometry and microstructure of bone, not only density.[1] The focal thinning of cortical bone associated with aging in post-menopausal osteoporotic bone in the proximal femur may predispose a hip to fracture.[2, 3] As the trabecular bone is lost with progression of osteoporosis, the remaining cortical bone take more predominant role on bone strength.[4] To date, no effective osteoporotic agent was demonstrated to enhance both cortical geometric change and bone strength. Herein, we investigate the effect of Teriparatide (rhPTH(1–34)) on cortical bone at femoral diaphysis in OVX rat model. Twenty 12-week-old, female Sprague Dawley rats were used in this study. Bilateral ovariectomies were performed in 16 animals and randomly divided to three groups as control (N=6), OVX (N=6) and treatment group after OVX (OVX+F) by teriparatide (N=8). After twelve weeks of intervention, all rats were euthanized and right femurs and L5 vertebrae were extracted for further tests. All bone specimens were subjected to dual-energy X-ray absorptiometer (DXA) to evaluate areal bone mineral density (aBMD) of L5 vertebrae and femurs, micro-computed tomography (micro-CT) to analyze cortical bone parameters of femoral diaphysis, including cortical cross section area (CSA), cortical thickness and cross-sectional moment of inertia (CSMI). A three-point bending test was applied to determine fracture load of each femurs. Compare to OVX group, increase of aBMD by 14.6 % at L5 vertebrae and 13.3% at femoral diahpysis in treatment group. The cortical parameters of femoral diaphysis, CSA and cortical thickness, analyzed by micro-CT were significantly increased but the increasing tendency of CSMI did not have significant changes statistically after teriparatide intervention for 3 months duration. The increase of cortical bone strength (OVX vs OVX+F group, 120.72±2.72 vs 137.93±5.02, p < 0.05) at femoral diaphysis after treatment were also noticed. This study has point out a deeper look at geometric change of cortical bone after teriparatide treatment. This finding imply teirparatide has the ability to change the geometry of cortical bone and increase bone strength at femoral diaphysis

In Italy the osteoporosis cause approximately 250000 fracture/year. A useful aid in the treatment of this pathology comes from the Teriparatide, a synthetic form of the natural human parathyroid hormone, that stimulates the formation of new bone by increasing the number and action of bone-forming cells, unlike estrogen and bisphosphonate which are only able in slowing or stopping bone loss by blocking the action of osteoclasts. The Authors presents theirs first results after treatment with 20 mcg per day of Forsteo (Ely Lilly), trade name of the teriparatide, along with calcium (1000mg) and vitamin D (400UI) supplementation, for the previewed maximum period of 18 months, in women older than 65 years with unsatisfactory bisphosphonate treatment, T-score equal or inferior to −4, multiple vertebral osteoporotic fractures and one or more age-independent factors risk like: BMI< 19 kg/m2, maternal familiarity with neck-femoral fractures before 65 years old, premature menopause, conditions associated with the extended immobility. The treatment induced in all patients an increase of Ca plasmatic concentrations for 16–24 hours with a maximum peak in 4–6 hours. Condition like hypercalcemia, severe renal insufficiency, renal calculosis, hyperpara-thyroidism, Paget, alkaline hyperphosphatasaemia and previous therapy radiating are the main parameter of exclusion from the treatment

Background: Despite of advanced implant modifications and surgical techniques, internal fixation of proximal femur fractures in osteoporotic elderly is conditioned by high rate of complicated healing and implant failure. The deterioration in micro architecture and the loss in mechanical properties of trabecular bone due to impaired bone turnover must be treated. Teriparatide(TPTD) has been demonstrated to improve of new bone formation in both trabecular and cortical envelopes and thus bone strength. Moreover in a number of fracture models on anims stimulates the healing process generating larger total callus volume. The aim of this study was to determine if bone anabolic agent (TPTD) may enhance the repair of femoral neck fractures in osteoporotic elderly synthesized with internal fixation and prevent complications.

Study Design: 31 compliant females between 57 and 95 years-old presenting a lateral femoral neck fracture was considered. At admission in orthopaedic unit they were undergone to haematochemical exams extended to bone turnover markers, lumbar and contralateral femoral BMD measured by DXA and x-rays of dorsal-lumbar spine. They were divided in two subgroups on the basis of concomitant vertebral compression fracture (VCF) discovered. To the patients with VCF was administrated daily subcutaneous injection of 20 microgr. of TPTD (TPTD group). Both groups received 1g of calcium carbonate and 1200 IU of colecalciferol daily from the first post-operative week. All the patients repeated x-rays of affected segments and bone turnover markers at 1,3,6 months. The pain was detected through a self-reported visual analogue scale (VAS). The functional outcome was evaluated in term of hospitalization, of walking on two crutches and their abandon.

Results: At admission serum 25(OH) vitamin D concentration was at lower levels but the supplementation was sufficient to normalize even if in TPTD group it remained lower than control. In TPTD group the bone formation markers were significantly increased at 1st month and peaked at 3rd month without an increase in bone resorption markers. In TPTD group the callus formation was radiologically evident from 1st month followed by consolidation within 3rd month for all. While in control group the fracture repair was less detectable at 3rd month with heterogeneous trend: one needed a re-operation, four were afflicted by delayed union and another one by VCF. Moreover earlier walking and abandon of crutches in TPTD group was related to significant decrease of pain. At 6th month BMD is significantly increased only in TPTD group.

Conclusions: In osteoporotic femoral neck fractures the demonstration of enhanced repair, the stability of the osteosynthesis, the pain relief and the recovery of autonomy in walking obtained with adjuvant anabolic therapy (TPTD) opens new therapeutic perspectives.

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 teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659–667

Bone strength is influenced by bone quality besides its density. This study aimed to evaluate the effects of teriparatide on changes of bone strength as well as trabecular and cortical bone microstructures at femoral neck in female ovariectomized (OVX) rats. Eighteen female Wister rats were divided into three groups: the sham control, OVX and treatment (Tx) groups. All of them were sacrificed after 3-month intermittent teriparatide intervention in Tx group. All left femurs were removed and scanned using micro-CT and followed by mechanical test for each femoral neck. Regarding micro-CT, four trabecular parameters including bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp), and trabecular number (TbN) and three cortical parameters including volumetric bone mineral density (vBMD), cortical cross-sectional area (CtAr) and cortical thickness (CtTh) were measured at femoral neck region. All data were analyzed and was presented as median ± SEM. The mean bone strength of femoral neck significantly decreased in OVX group when compared to the control group (p < 0.05) and was significantly restored in Tx group (p < 0.01). Regarding the trabecular parameters, the BV/TV and TbTh significantly decreased in OVX group while compare to Tx group. However, no significant difference was observed in TbSp and TbN between the groups. Regarding the cortical parameters, CtTh was significantly greater in Tx group than that in OVX group (p<0.01). As our findings, intermittent teriparatide can improve the deteriorated bone strength of femoral neck due to ovarian deficiency via changing both trabecular microarchitecture and cortical morphology

The December 2015 Spine Roundup360 looks at: Ketamine in scoliosis surgery; Teriparatide in osteoporotic spinal fractures; Trabecular metal in the spine?; Revision surgery a SPORTing chance?; The course of degenerative lumbar spondylolisthesis; Hip or lumbar spine: a common conundrum

Introduction: Between the elderly affected by femoral neck or diaphyseal fractures are emerging few serious complications as delate union, instability of osteosynthesis, re-fracture or periprosthetic fracture. In addition the co-morbidity elevate ulteriorly the risks of the new operation which is often impossible or refused. Recently it has been recommended to orthopaedic surgeons the managment and treatment of osteoporosis. The aim of this study was to consider at 2 years follow-up the functional outcome of femoral fracture in osteoporotic elderly treated with a surgical procedure followed by daily assumption of teriparatide, an anabolic agent increasing bone mineral content, density and strength. Materials and Methods: 21 compliant female between 63 and 94 years-old presenting a femoral fracture were recruited. Before operation they undergone to a routinary instrumental examins completed by bone metabolism screening. This was constituted by biochemical bone turnover markers, standard radiograms of dorsal and lumbar spine. Lumbar and contralateral femoral BMD was measured by DXA during hospitalization before the assumption of anabolic agent. They received daily subcutaneous teriparatide (20 microg) per day for 18 months, 1g of calcium and 800 UI of vitamin D3 daily as oral supplementation from day 15 by operation. All the patients repeated: xrays of affected segment at 2, 4, 6 months; biochemical bone markers 1, 3, 6, 12, 18 and 24 months; DEXA at first and second year. The evaluation of the quality of life was evaluated in terms of recovery of walking, need of re.operation, occurance of new fracture and with a questionnaire. Results: eleven lateral femoral neck fracture treated with endomedullary nail, six medial femoral neck fracture treated with cemented endoprosthesis, four periprosthetic fracture of the femur treated with plaque and screws. The healing was detected with radiograms before 4th month. The vitamin D was at lower levels at admission but the supplementation was sufficient to normalize. The other biochemical variables of bone formation and resorption peaked within the consolidation process then remained normalized for two years. Lumbar and contralateral femoral BMD were increased after 12 months and maintained at 24 months. At 2 years follow-up all patients live, walk in autonomy without or with stick and none of them have needed a re-operation or was afflicted by new vertebral or non vertebral fracture. Conclusions: The clinical relevance of the present study is the significant improvement of functional outcome and quality of life after femoral fracture in osteoporotic elderly with post-operative assumption of anbolic agent as Teriparatide

Aims

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.

Parathyroid hormone (PTH) and derivatives such as teriparatide (PTH (1–34)) have gained major attention in recent years in treatment of osteoporosis due to their anabolic action on the bone remodelling cycle. These drugs are currently the only available agents being classified as sole anabolic. Interestingly, action of these agents strongly depends on the way they are administered. While these drugs act catabolically when given continuously, they act anabolically when administered in a pulsatile way. Several hypotheses have been proposed to explain this behaviour. However, so far no agreement as regards detailed underlying biochemical regulation has been made. Parallel to intense experimental research to resolve this problem a few mathematical models have been proposed dealing with this subject. In this paper we propose a novel underlying mechanism for anabolic action of PTH based on mathematical modelling of bone cell population dynamics. Using this model allows us to investigate various hypotheses put forward by bone biologists. Additionally, comparison with other theoretical models proposed in the literature will be made

Aims

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.

Aims

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.

Aims

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.

Aims

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.

Aims

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).

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.

Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1.

Objectives

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.

Objectives

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.