Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review.

Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. BACKGROUND: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. METHODS: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). RESULTS: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. CONCLUSION: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved.

Analgesic effect of nasal salmon calcitonin during the early post-fracture period of the distal radius fracture.

OBJECTIVES: To investigate the analgesic effect of nasal salmon calcitonin on the post-fracture period of distal radius fracture. METHODS: In this prospective randomized double-blind study, forty-one postmenopausal women with a recent distal radius fracture treated conservatively were randomly assigned to receive either 200 IU of intranasal salmon calcitonin or placebo daily for 3 months following fracture. The assessment of the patient's pain was recorded using the Visual Analogue Scale (VAS). RESULTS: The average age of the calcitonin group was 67.11 (SD, ±8.68) years and 64.91 (SD, ±7.48) of the placebo group. In the calcitonin group, the mean VAS score improved from 4.05 to 0.53 while in the placebo group from 3.36 to 0.32. A higher decrease of VAS score during the first post-fracture period was observed in the calcitonin group. CONCLUSIONS: In the study, there is a statistically significant calcitonin mediated analgesic effect in the immediate post fracture period (at 10 days) when compared to placebo group. These results are in accordance with literature referring to the analgesic effect of calcitonin in the acute osteoporotic vertebral compression fracture. Thus calcitonin administration could be recommended to a short term course in acute osteoporotic conservatively treated distal radius fractures.

Cost-effective osteoporosis treatment thresholds in Greece.

UNLABELLED: A Greek-specific cost-effectiveness analysis determined the FRAX-based intervention thresholds. Assuming a willingness to pay of 30,000 , osteoporosis treatment is cost-effective in subjects under the age of 75 with 10-year probabilities for hip and major osteoporotic fractures of 2.5 and 10 %, respectively, while for older patients, the same thresholds are raised to 5 and 15 %. INTRODUCTION: The purpose of this study was to determine the FRAX calculated fracture probabilities at which therapeutic intervention can be considered as cost-effective in the Greek setting. METHODS: A Markov cohort model was populated with Greek data, and quality-adjusted life years (QALYs) were used to calculate the cost-effective thresholds for an annual medication cost of 733.7 by gender and age. Average FRAX-based 10-year probabilities for both major osteoporotic and hip fractures were multiplied by the model-derived relative risk at which a cost of 30,000 for each QALY gained was observed for treatment versus to no intervention. RESULTS: A biphasic intervention threshold model is supported by our findings. Osteoporosis treatment becomes cost-effective when absolute 10-year probabilities for hip and major osteoporotic fractures reach 2.5 and 10 %, respectively, among both men and women under the age of 75. For older subjects, the proposed intervention thresholds are raised to 5 and 15 % 10-year probability for hip and major osteoporotic fractures, respectively. CONCLUSIONS: Cost-effective osteoporosis treatment may be facilitated in Greece if FRAX algorithm is used to identify subjects with 10-year probabilities for hip and major osteoporotic fractures of 2.5 and 10 %, under the age of 75, while for older patients, the relevant thresholds are 5 and 15 %, respectively.

Management of bisphosphonate-related osteonecrosis of the jaw: a literature review.

Osteonecrosis of the jaw (ONJ) is a serious side effect of bisphosphonate use in patients with osteoporosis, Paget's disease, hypercalcemia of malignancy, metastatic bone disease and multiple myeloma, although recently this complication has also been reported in patients under non-bisphosphonate medication, such as denosumab and bevacizumab. The occurrence of ONJ is higher in oncology patients treated with high-dose iv bisphosphonates than in osteoporosis patients treated with oral bisphosphonates. Although multiple hypotheses have been proposed, the exact pathogenic mechanism of ONJ still remains unclear. As treatment protocols based on randomized controlled trials (RCTs) do not exist, we critically reviewed the existing data concerning the management of bisphosphonate-related osteonecrosis of the jaw, including the most recent data for the use of teriparatide and hyperbaric oxygen.

Incidence of hip fractures in Greece during a 30-year period: 1977-2007.

UNLABELLED: The incidence of hip fractures doubled in Greece from 1977 to 2007 among people aged 50 and over. A mild decrease was observed after 2002, although the future trend cannot be safely anticipated at the moment. Half of all hip fractures in 2007 were derived from the age group of 80 and over. INTRODUCTION: The purpose of this study was to determine the incidence of hip fractures during a 30-year period in Greece among people aged 50 and over and to document possible alterations in secular trends. METHODS: We studied hip fractures during 2007 and compared them with those of previous years starting from 1977 with an in-between 5-year interval (1977, 1982, 1987, 1992, 1997, 2002). Age- and sex-specific incidence was calculated, and secular trends were recorded. The relative risk of hip fracture in every age group was estimated according to the corresponding incidence of 1977. RESULTS: The adjusted incidence of hip fractures increased approximately 100 % throughout the study; it progressively increased from 1977 to 2002 and exhibited a mild significant decrease thereafter. The relative risk of hip fractures among subjects aged 60-69 in 2007 has declined compared with 1977 [0.85, 95 % confidence intervals (CI) 0.79-0.92, p < 0.0005]. Among people aged 70-79, an increased relative fracture risk (1.53, 95 % CI 1.45-1.61, p < 0.0005) was estimated in 2007 compared with 1977. People ≥80 years old were responsible for half of the hip fractures in 2007 but only for the 22.5 % of fractures in 1977. The relative fracture risk in people aged ≥80 was 2.81 times higher (95 % CI 2.64-2.98, p < 0.0005) in 2007 than in 1977. CONCLUSIONS: The incidence of hip fractures doubled during the last 30 years among people aged ≥50 years, although a mild decrease was observed in almost all age groups after 2002. The most affected group is 80 and over.

Balloon kyphoplasty and vertebroplasty in the management of vertebral compression fractures.

Vertebral compression fractures (VCFs) are the most prevalent fractures in osteoporotic patients. The classical conservative management of these fractures is through rest, pain medication, bracing and muscle relaxants. The aim of this paper is to review prospective controlled studies comparing the efficacy and safety of minimally invasive techniques for vertebral augmentation, vertebroplasty (VP) and balloon kyphoplasty (BKP), versus non-surgical management (NSM). The Fracture Working Group of the International Osteoporosis Foundation conducted a literature search and developed a review paper on VP and BKP. The results presented for the direct management of osteoporotic VCFs focused on clinical outcomes of these three different procedures, including reduction in pain, improvement of function and mobility, vertebral height restoration and decrease in spinal curvature (kyphosis). Overall, VP and BKP are generally safe procedures that provide quicker pain relief, mobility recovery and in some cases vertebral height restoration than conventional conservative medical treatment, at least in the short term. However, the long-term benefits and safety in terms of risk of subsequent vertebral fractures have not been clearly demonstrated and further prospective randomized studies are needed with standards for reporting. Referral physicians should be aware of VP/BKP and their potential to reduce the health impairment of patients with VCFs. However, VP and BKP are not substitutes for appropriate evaluation and treatment of osteoporosis to reduce the risk of future fractures.

Factors influencing bone loss in paraplegia.

BACKGROUND AND AIM: Significant bone loss develops in the first months and continues years after spinal cord injury. A cross - sectional comparative study was performed to evaluate factors influencing bone loss in spinal cord injured men with paraplegia. PATIENTS AND METHODS: We studied 31 paraplegic men in chronic stage (>1.5 years) in comparison with 30 able-bodied men of similar age, height, and weight. The paraplegic men were allocated into 2 subgroups based on the neurological level of injury; high paraplegics (n=16, T4-T7 neurological level of injury) and low paraplegics (n=15, T8-T12 neurological level of injury). The influence of positive and negative factors (spasticity, standing-therapeutic walking, and duration of paralysis) on bone structures was evaluated by pQCT measurement of the total, trabecular and cortical bone mineral density (BMDtot, BMDtrab, BMDcort, respectively) and cortical thickness (THIcort) at the distal tibial epiphysis and the tibial diaphysis at 4% and 38% proximal to the distal end of the tibia. The stress strain index (SSI) was measured at 14% (SSI(2)) and at 38% (SSI(3)) of the tibial diaphysis, and the difference SSI(3) - SSI(2) (δSSI(3-2)) was calculated. RESULTS: In all paraplegics, bone mineral density parameters were significantly reduced compared to the control group (BMDtot: p<0.0005, BMDtrab: p<0.0005, BMDcort: p=0.029, THIcort: p=0.019, SSI(2): p=0.009, SSI(3): p=0.003, respectively). Paraplegics who used standing frames or long brace orthoses had statistically significant higher bone mass and geometric parameters (BMDtrab: p=0.03, BMDtot: p=0.01, THIcort: p=0.013, respectively), while spasticity did not protect bone. The duration of paralysis was significantly related to trabecular bone loss (r=-0.5, p=0.05) and cortical thickness (r=-0.6, p=0.006) in high paraplegics and to δSSI(3-2) in low paraplegics (r=0.534, p=0.03). CONCLUSIONS: The neurological level of injury adversely affects bone strength in paralyzed lower extremities such as the distal tibia. Standing or therapeutic walking could possibly have a positive effect in cortical and trabecular bone in paraplegia.

Seasonal variations of vitamin D status in Greek postmenopausal women receiving enriched dairy products for 30 months: the Postmenopausal Health Study.

The effectiveness of a 30-month dietary intervention on vitamin D status of Greek postmenopausal women was examined. Sixty-six postmenopausal women (55-65 years old) were randomized into an intervention group (IG), receiving a daily dose of 7.5 µg of vitamin D3 for 12 months that increased to 22.5 µg for the remaining 18 months of intervention through fortified dairy products and attending nutrition and lifestyle counselling sessions, and a control group (CG). After 30 months of intervention, during winter, serum 25-hydroxy vitamin D (25(OH)D) levels significantly decreased in the CG while remained in the same high levels as in the summer period in the IG. Similarly, at 30 months of intervention the prevalence of vitamin D insufficiency was significantly higher in the CG compared to the IG (60.0 vs 25.0%, P = 0.006). In conclusion, the current intervention scheme with a daily dose of 22.5 µg of Vitamin D could significantly decrease the prevalence of vitamin D insufficiency during winter time but not entirely prevent it.

Decreased tibial bone strength in postmenopausal women with aseptic loosening of cemented femoral implants measured by peripheral quantitative computed tomography (pQCT).

Aseptic loosening after total hip arthroplasty is related to bone loss of the operated leg. The aim of the present study was to investigate the effect of aseptic loosening on volumetric bone mineral density (vBMD) and bone geometry in the operated leg, in postmenopausal women with a loosened cemented femoral implant using peripheral quantitative computed tomography (pQCT). We matched 12 postmenopausal women with aseptic loosening of cemented femoral implant, with 12 women without aseptic loosening (control group) according to age, BMI, and years from operation. All patients underwent pQCT of both tibias, DXA of the lumbar spine, and determination of biochemical markers of bone turnover. pQCT values in the control group as well as the nonoperated legs between groups had no significant difference. In the aseptic loosening group, there was significant reduction of cortical vBMD (cort vBMD) at 14% and 38% sites (cortical site), cortical thickness at 38% site, and of polar stress strength index (SSIp) at 14% site (transition zone) in the operated compared with the nonoperated leg. Similarly, there was significant reduction of cort vBMD at 14% and 38% sites and total vBMD and trabecular vBMD (trab vBMD) at the 14% site in the operated legs between the two groups. The aseptic loosening group had increased osteocalcin and serum collagen cross-linked N- and C-telopeptides (sNTX and sCTX) levels compared with controls. Aseptic loosening is associated with significant decrease of cortical and trabecular vBMD, and impairment of bone geometry and strength only in the operated leg. Increased bone turnover probably represents a local phenomenon, and is not associated with systemic skeletal disease.

Effect of rhythmic gymnastics on volumetric bone mineral density and bone geometry in premenarcheal female athletes and controls.

CONTEXT AND OBJECTIVE: Weight-bearing exercise during growth exerts positive effects on the skeleton. Our objective was to test the hypothesis that long-term elite rhythmic gymnastics exerts positive effects on volumetric bone mineral density and geometry and to determine whether exercise-induced bone adaptation is associated with increased periosteal bone formation or medullary contraction using tibial peripheral quantitative computed tomography and bone turnover markers. DESIGN AND SETTING: We conducted a cross-sectional study at a tertiary center. SUBJECTS: We studied 26 elite premenarcheal female rhythmic gymnasts (RG) and 23 female controls, aged 9-13 yr. MAIN OUTCOME MEASURES: We measured bone age, volumetric bone mineral density, bone mineral content (BMC), cortical thickness, cortical and trabecular area, and polar stress strength index (SSIp) by peripheral quantitative computed tomography of the left tibia proximal to the distal metaphysis (trabecular) at 14, 38 (cortical), and 66% (muscle mass) from the distal end and bone turnover markers. RESULTS: The two groups were comparable according to height and chronological and bone age. After weight adjustment, cortical BMC, area, and thickness at 38% were significantly higher in RG (P < 0.005-0.001). Periosteal circumference, SSIp, and muscle area were higher in RG (P < 0.01-0.001). Muscle area was significantly associated with cortical BMC, area, and SSIp, whereas years of training showed positive association with cortical BMC, area, and thickness independent of chronological age. CONCLUSIONS: RG in premenarcheal girls may induce positive adaptations on the skeleton, especially in cortical bone. Increased duration of exercise is associated with a positive response of bone geometry.

Calcitonin effect on Achilles tendon healing. An experimental study on rabbits.

OBJECTIVE: A positive potential effect of Calcitonin (CT) on Achilles tendon healing was investigated as well as the ability of MRI to follow the tendon healing process. MATERIALS AND METHODS: A standardized tenotomy of the Achilles tendon was performed on forty-two rabbits. Twenty-one animals received daily 21 IU /kg Calcitonin intramuscularly (treatment group CT) during the experiment and the remaining received saline solution (control group P). Seven animals from each group were killed at one, two and three weeks postoperatively. All animals had serial MRI scans and tendon samples underwent biomechanical and histological testing. RESULTS: For both groups, animals of the same subgroup showed statistically significant difference in signal intensity values of MRI between the 1st and 3rd week (p<0.001) and between the 2nd and 3rd week (p<0.001). Signal intensity values of MRI didn't show any differences between animals under treatment and controls measured at 1st (p=0.23), 2nd (p=0.23) and 3rd (p=0.53) postoperative week. Tendon samples from group CT showed statistically significant difference in ultimate tensile strength compared to controls at 2 (p<0,0005) and 3 (p<0,0005) weeks post-surgery. Histology showed a positive Calcitonin effect at all tendon healing stages. CONCLUSION: It is suggested that Calcitonin enhances Achilles tendon healing process.