Bilateral atypical insufficiency fractures of the proximal tibia and a unilateral distal femoral fracture associated with long-term intravenous bisphosphonate therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Atypical insufficiency fractures of the femur in patients on long-term bisphosphonate therapy have been well described in recent literature. The majority of cases are associated with minimal or no trauma and occur in the subtrochanteric or diaphyseal region.</p> <p>Case presentation</p> <p>We describe the case of a 76-year-old British Caucasian woman who presented initially to an emergency department and then to her primary care physician with a long-standing history of bilateral knee pain after minor trauma. Plain radiographs showed subtle linear areas of sclerosis bilaterally in her proximal tibiae. Magnetic resonance imaging confirmed the presence of insufficiency fractures in these areas along with her left distal femur. There are very few reports of atypical insufficiency fractures involving the tibia in patients on long-term bisphosphonate therapy and this appears to be the only documented bilateral case involving the metaphyseal regions of the proximal tibia and distal femur.</p> <p>Conclusion</p> <p>In addition to existing literature describing atypical fractures in the proximal femur and femoral shaft, there is a need for increased awareness that these fractures can also occur in other weight-bearing areas of the skeleton. All clinicians involved in the care of patients taking long-term bisphosphonates need to be aware of the growing association between new onset lower limb pain and atypical insufficiency fractures.</p

Five-year follow-up of Japanese patients with Paget's disease of the bone after treatment with low-dose oral alendronate: a case series

<p>Abstract</p> <p>Introduction</p> <p>Paget's disease of the bone is characterized by focal abnormalities of increased bone turnover affecting one or more sites throughout the skeleton. Although this disease is rare in Japan, it is common in western and southern Europe, and among British migrants in Australia and New Zealand. Bisphosphonates have been widely used for the treatment of Paget's disease of the bone and are considered to be the treatment of choice. However, there have been few reports on the long-term follow-up examination of patients after their treatment with bisphosphonates.</p> <p>Case presentation</p> <p>We report the treatment with a low dose of oral alendronate (5 mg per day) which was effective in reducing bone turnover and pain over the five-year follow-up period in two Japanese patients, a 66-year-old man and a 68-year-old woman, with Paget's disease of the bone. Furthermore, in one patient, no clinical symptoms, such as bone pain or increases in serum total alkaline phosphatase and urinary N-terminal telopeptide of type I collagen as markers of bone turnover, were observed over the patient's five-year follow-up period.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first report of a long-term follow-up of patients with Paget's disease of the bone after a six-month treatment with low-dose oral alendronate (5 mg per day).</p

Improvement of pain and regional osteoporotic changes in the foot and ankle by low-dose bisphosphonate therapy for complex regional pain syndrome type I: a case series

<p>Abstract</p> <p>Introduction</p> <p>Complex regional pain syndrome is characterized by pain, allodynia, hyperalgesia, edema, signs of vasomotor instability, movement disorders, joint stiffness, and regional osteopenia. It is recognized to be difficult to treat, despite various methods of treatment, including physiotherapy, calcitonin, corticosteroids, sympathetic blockade, and nonsteroidal anti-inflammatory drugs. Pathophysiologically, complex regional pain syndrome reveals enhanced regional bone resorption and high bone turnover, and so bisphosphonates, which have a potent inhibitory effect on bone resorption, were proposed for the treatment of complex regional pain syndrome.</p> <p>Case presentation</p> <p>A 48-year-old Japanese man with complex regional pain syndrome type I had severe right ankle pain with a visual analog scale score of 59 out of 100 regardless of treatment with physiotherapy and nonsteroidal anti-inflammatory drugs for five months. Radiographs showed marked regional osteoporotic changes and bone scintigraphy revealed a marked increase in radioactivity in his ankle. One month after the start of oral administration of risedronate (2.5 mg per day), his bone pain had fallen from a VAS score of 59 out of 100 to 18 out of 100. Bone scintigraphy at 12 months showed a marked reduction in radioactivity to a level comparable to that in his normal, left ankle. On the basis of these results, the treatment was discontinued at 15 months. At 32 months, our patient had almost no pain and radiographic findings revealed that the regional osteoporotic change had returned to normal.</p> <p>A second 48-year-old Japanese man with complex regional pain syndrome type I had severe right foot pain with a visual analog scale score of 83 out of 100 regardless of treatment with physiotherapy and nonsteroidal anti-inflammatory drugs for nine months. Radiographs showed regional osteoporotic change in his phalanges, metatarsals, and tarsals, and bone scintigraphy revealed a marked increase in radioactivity in his foot. One month after the start of oral administration of alendronate (35 mg per week), his bone pain had fallen from a visual analog scale score of 83 out of 100 to 30 out of 100 and, at nine months, was further reduced to 3 out of 100. The treatment was discontinued at 15 months because of successful pain reduction. At 30 months, our patient had no pain and the radiographic findings revealed marked improvement in regional osteoporotic changes.</p> <p>Conclusions</p> <p>We believe low-dose oral administration of bisphosphonate is worth considering for the treatment of idiopathic complex regional pain syndrome type I accompanied by regional osteoporotic change.</p

The impact of vitamin D status on changes in bone mineral density during treatment with bisphosphonates and after discontinuation following long-term use in post-menopausal osteoporosis

BACKGROUND: It is still unclear whether addition of calcium/vitamin D supplements leads to an incremental benefit in patients taking bisphosphonates and whether achievement of serum level of 25 (OH) vitamin D of at least 70 nmol/L has an impact on the skeletal response to bisphosphonates. Moreover the maintenance of BMD after bisphosphonates withdrawal with the continuation of calcium/vitamin D supplements only, remains uncertain. The aims were to assess the impact of vitamin D status on changes in bone mineral density (BMD) in firstly patients with post-menopausal osteoporosis on bisphosphonates and secondly following discontinuation of bisphosphonates after long-term use. METHODS: Two patient groups were recruited. The first study population comprised of 112 women treated with a bisphosphonate. The second study population consisted of 35 women who had been on bisphosphonates for > 5 years in whom the treatment agent was discontinued. Baseline BMD, changes in BMD following treatment, duration of treatment, serum 25 (OH) vitamin D, parathyroid hormone (PTH), urine C-terminal telopeptides of type 1 collagen (CTX) were obtained on the study participants. RESULTS: In the first study group, subjects with serum vitamin D concentrations (> 70 nmol/L) had a significantly lower serum PTH level (mean [SEM] 41 [2] ng/L). PTH concentrations of 41 ng/L or less was associated with a significantly higher increase in BMD at the hip following treatment with bisphosphonates compared to patients with PTH > 41 ng/L (2.5% [0.9] v/s -0.2% [0.9], P = 0.04). In the second study group, discontinuation of bisphosphonate for 15 months after long-term treatment did not result in significant bone loss at the lumbar spine and total hip, although a trend towards gradual decline in BMD at the femoral neck was observed. CONCLUSION: the data suggest that optimal serum 25 (OH) vitamin D concentration may lead to further reduction in bone loss at the hip in patients on bisphosphonates. A prospective controlled trial is needed to evaluate whether the response to bisphosphonates is influenced by vitamin D status. BMD is preserved at the lumbar spine and total hip following discontinuation of bisphosphonate for a short period following long-term treatment, although a gradual loss occurs at the femoral neck

Effect of Longâ Term Oral Bisphosphonates on Implant Wound Healing: Literature Review and a Case Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141603/1/jper0584.pd

Temporal Trends in Vertebral Size and Shape from Medieval to Modern-Day

Human lumbar vertebrae support the weight of the upper body. Loads lifted and carried by the upper extremities cause significant loading stress to the vertebral bodies. It is well established that trauma-induced vertebral fractures are common especially among elderly people. The aim of this study was to investigate the morphological factors that could have affected the prevalence of trauma-related vertebral fractures from medieval times to the present day. To determine if morphological differences existed in the size and shape of the vertebral body between medieval times and the present day, the vertebral body size and shape was measured from the 4th lumbar vertebra using magnetic resonance imaging (MRI) and standard osteometric calipers. The modern samples consisted of modern Finns and the medieval samples were from archaeological collections in Sweden and Britain. The results show that the shape and size of the 4th lumbar vertebra has changed significantly from medieval times in a way that markedly affects the biomechanical characteristics of the lumbar vertebral column. These changes may have influenced the incidence of trauma- induced spinal fractures in modern populations

Effect of Ibandronate on Bending Strength and Toughness on Rodent Cortical bone; possible implications for fracture prevention

OBJECTIVES: There remains conflicting evidence regarding cortical bone strength following bisphosphonate therapy. As part of a study to assess the effects of bisphosphonate treatment on the healing of rat tibial fractures, the mechanical properties and radiological density of the uninjured contralateral tibia was assessed. METHODS: Skeletally mature aged rats were used. A total of 14 rats received 1µg/kg ibandronate (iban) daily and 17 rats received 1 ml 0.9% sodium chloride (control) daily. Stress at failure and toughness of the tibial diaphysis were calculated following four-point bending tests. RESULTS: Uninjured cortical bone in the iban group had a significantly greater mean (standard deviation (sd)), p < 0.001, stress at failure of 219.2 MPa (sd 45.99) compared with the control group (169.46 MPa (sd 43.32)) following only nine weeks of therapy. Despite this, the cortical bone toughness and work to failure was similar. There was no significant difference in radiological density or physical dimensions of the cortical bone. CONCLUSIONS: Iban therapy increases the stress at failure of uninjured cortical bone. This has relevance when normalising the strength of repair in a limb when comparing it with the unfractured limb. However, the 20% increase in stress at failure with iban therapy needs to be interpreted with caution as there was no corresponding increase in toughness or work to failure. Further research is required in this area, especially with the increasing clinical burden of low-energy diaphyseal femoral fractures following prolonged use of bisphosphonates. Cite this article: Bone Joint Res 2015;4:99–10

Treatment of OPG-deficient mice with WP9QY, a RANKL-binding peptide, recovers alveolar bone loss by suppressing osteoclastogenesis and enhancing osteoblastogenesis.

Osteoblasts express two key molecules for osteoclast differentiation, receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG), a soluble decoy receptor for RANKL. RANKL induces osteoclastogenesis, while OPG inhibits it by blocking the binding of RANKL to RANK, a cellular receptor of RANKL. OPG-deficient (OPG–/–) mice exhibit severe alveolar bone loss with enhanced bone resorption. WP9QY (W9) peptide binds to RANKL and blocks RANKL-induced osteoclastogenesis. W9 is also reported to stimulate bone formation in vivo. Here, we show that treatment with W9 restores alveolar bone loss in OPG–/–mice by suppressing osteoclastogenesis and enhancing osteoblastogenesis. Administration of W9 or risedronate, a bisphosphonate, to OPG–/–mice significantly decreased the osteoclast number in the alveolar bone. Interestingly, treatment with W9, but not risedronate, enhanced Wnt/β-catenin signaling and induced alveolar bone formation in OPG–/–mice. Expression of sclerostin, an inhibitor of Wnt/β-catenin signaling, was significantly lower in tibiae of OPG–/–mice than in wild-type mice. Treatment with risedronate recovered sclerostin expression in OPG–/–mice, while W9 treatment further suppressed sclerostin expression. Histomorphometric analysis confirmed that bone formation-related parameters in OPG–/–mice, such as osteoblast number, osteoblast surface and osteoid surface, were increased by W9 administration but not by risedronate administration. These results suggest that treatment of OPG–/–mice with W9 suppressed osteoclastogenesis by inhibiting RANKL signaling and enhanced osteoblastogenesis by attenuating sclerostin expression in the alveolar bone. Taken together, W9 may be a useful drug to prevent alveolar bone loss in periodontitis