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.

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.

Management of osteoporosis in the elderly.

BACKGROUND: Osteoporosis is predominantly a condition of the elderly, and the median age for hip fracture in women is approximately 83 years. Osteoporotic fracture risk is multifactorial, and often involves the balance between bone strength and propensity for falling. OBJECTIVE: To present an overview of the available evidence, located primarily by Medline searches up to April, 2009, for the different management strategies aimed at reducing the risk of falls and osteoporotic fractures in the elderly. RESULTS: Frailty is an independent predictor of falls, hip fractures, hospitalisation, disability and death in the elderly that is receiving increasing attention. Non-pharmacological strategies to reduce fall risk can prevent osteoporotic fractures. Exercise programmes, especially those involving high doses of exercise and incorporating balance training, have been shown to be effective. Many older people, especially the very elderly and those living in care institutions, have vitamin D inadequacy. In appropriate patients and given in sufficient doses, vitamin D and calcium supplementation is effective in reducing both falls and osteoporotic fractures, including hip fractures. Specific anti-osteoporosis drugs are underused, even in those most at risk of osteoporotic fracture. The evidence base for the efficacy of most such drugs in the elderly is incomplete, particularly with regard to nonvertebral and hip fractures. The evidence base is perhaps most complete for the relatively recently introduced drug, strontium ranelate. Non-adherence to treatment is a substantial problem, and may be exacerbated by the requirements for safe oral administration of bisphosphonates. CONCLUSION: Evidence-based strategies are available for reducing osteoporotic fracture risk in the elderly, and include exercise training, vitamin D and calcium supplementation, and use of evidence-based anti-osteoporotic drugs. A positive and determined approach to optimising the use of such strategies could reduce the burden of osteoporotic fractures in this high-risk group.

Changes in biochemical indices of bone metabolism in post-menopausal women following a dietary intervention with fortified dairy products.

BACKGROUND: In southern Europe, calcium supplementation alone is a common practice for osteoporosis prevention. The present study aimed to examine whether calcium supplementation alone could be as effective in achieving favourable changes on bone metabolism indices of Greek post-menopausal women as a holistic dietary approach combining consumption of dairy products fortified with calcium and vitamin D(3) and nutrition counselling sessions for five winter months. METHODS: A sample of 101 post-menopausal women was randomised to a dairy intervention group (IG: n = 39), receiving approximately 1200 mg of calcium and 7.5 microg of vitamin D(3) per day via fortified dairy products and attending biweekly nutrition counselling sessions; a calcium-supplemented group (SG: n = 26) receiving a total of 1200 mg calcium per day; and a control group (CG: n = 36). RESULTS: Regarding insulin-like growth factor (IGF)-I, a higher increase was observed for the IG compared to the changes in the CG and the SG (P = 0.049). Regarding serum parathyroid hormone (PTH) levels, the increase observed in the CG was higher than the changes observed in the other two groups but the differences were of marginal significance (P = 0.055). No significant differences were observed among groups regarding the changes in serum osteocalcin and type I collagen cross-linked C-telopeptide levels. CONCLUSIONS: The application of a holistic intervention approach combining nutrition counselling and consumption of fortified dairy products for five winter months induced some more favourable changes in IGF-I and PTH levels compared to calcium supplementation alone. Intervention periods longer than 5 months might be required to achieve significant differences among groups for bone remodelling biomarkers as well.

Post-fracture management of patients with hip fracture: a perspective.

BACKGROUND: Hip fracture creates a worldwide morbidity, mortality and economic burden. After surgery, many patients experience long-term disability or die as a consequence of the fracture. A fracture is a major risk factor for a subsequent fracture, which may occur within a short interval. METHODS: A literature search on post-fracture management of patients with hip fracture was performed on the Medline database. Key experts convened to develop a consensus document. FINDINGS: Management of hip-fracture patients to optimize outcome after hospital discharge requires several stages of care co-ordinated by a multidisciplinary team from before admission through to discharge. Further studies that specifically assess prevention and post-fracture management of hip fracture are needed, as only one study to date has assessed an osteoporosis medication in patients with a recent hip fracture. Proper nutrition is vital to assist bone repair and prevent further falls, particularly in malnourished patients. Vitamin D, calcium and protein supplementation is associated with an increase in hip BMD and reduction in falls. Rehabilitation is essential to improve functional disabilities and survival rates. Fall prevention and functional recovery strategies should include patient education and training to improve balance and increase muscle strength and mobility. Appropriate management can prevent further fractures and it is critical that high-risk patients are identified and treated. To foster this process, clinical pathways have been established to support orthopaedic surgeons. CONCLUSION: Although hip fracture is generally associated with poor outcomes, appropriate management can ensure optimal recovery and survival, and should be prioritized after a hip fracture to avoid deterioration of health and prevent subsequent fracture.

Protective effect of plant extract from Onobrychis ebenoides on ovariectomy-induced bone loss in rats.

OBJECTIVE: Certain plant extracts have been the object of recent studies due to their mild estrogenic action and their possible potential role in osteoporosis prevention and/or treatment. The present study was undertaken to investigate the possible protective effect of the aqueous solution of the plant Onobrychis ebenoides, with proven in vitro mild estrogenic action, on bone mass loss of the ovariectomized (Ovx) rat experimental model of osteoporosis. METHODS: Forty intact female mature (10-month-old) Wistar rats were separated into three groups: Ovx, Ovx plus plant extract (Ph) and sham-operated (control). Ph administration in the drinking water at a dose of 300 mg/kg body weight/day commenced immediately after Ovx. Bone mineral density (BMD) values, percentage change from the baseline measurement and histomorphometry of the tibia, as well as body and uterine weight, were examined and compared between groups. RESULTS: Comparison of BMD absolute values of the whole tibia of Ovx + Ph and Ovx animals at both 3 and 6 months post-Ovx were highly significant (p < 0.0005), showing a protective effect on treated animals. The extract did not appear to have such a beneficial effect on BMD of the proximal tibia of the treated animals compared to the Ovx animals after 3 months; however, a significant protective effect was observed at 6 months post-Ovx in treated animals compared to the Ovx (p = 0.015). When the % changes from baseline measurement of the whole tibia of Ovx + Ph and controls were compared, there was no significant difference at 3 or 6 months, demonstrating a highly protective effect; the respective comparisons of proximal tibia % changes did not display such protection. Body and uterine weight comparisons showed no significant difference between Ovx and treated rats, whereas, the level of significance for each group compared to controls was p < 0.0005. CONCLUSIONS: The Ph studied showed a highly significant protective effect on BMD of the whole tibia of Ovx rats after 3 and 6 months of treatment, compared to the non-treated animals. Its effect on the proximal tibia was less pronounced, but also statistically significant compared to non-treated rats after 6 months. The lack of significant effect on body and uterine weight is in favor of its selective estrogen receptor modulator-like activity, and merits further studies.

Effect of intermittent administration of 200 IU intranasal salmon calcitonin and low doses of 1alpha(OH) vitamin D3 on bone mineral density of the lumbar spine and hip region and biochemical bone markers in women with postmenopausal osteoporosis: a pilot study.

A 1-year prospective, open, randomized, controlled trial was conducted as a pilot study to examine the effect of intermittent administration of 200 IU intranasal salmon calcitonin and 1alpha(OH) vitamin D3 [1alpha(OH)D3] on bone mineral density (BMD) of the lumbar spine and hip as well as on the markers of bone metabolism in women with postmenopausal osteoporosis. A total of 102 randomly recruited women received either 200 IU intranasal salmon calcitonin (Miacalcic nasal 200, Novartis, Basel, Switzerland) daily, 1 month on-1 month off, 0.25 mug 1alpha(OH)D3, and 500 mg elemental calcium continuously (n=57 women) or only 0.25 mug 1alpha(OH)D3 and 500 mg calcium (n=45 women) for a period of 1 year. BMD of the lumbar spine and hip plus biochemical markers reflecting calcium (Ca) metabolism and bone turnover [serum Ca, serum phosphorus, intact parathormone (iPTH), total and bone-specific alkaline phosphatase, osteocalcin levels, 24-h urinary Ca, morning fasting urinary Ca/creatinine, and Pyrilinks-D/creatinine ratio] were measured at the beginning of the study before treatment and after 6 and 12 months of treatment. Baseline characteristics of participants, including age, body mass index, lumbar and hip BMD, and biochemical markers were similar between the two groups. A total of 91 patients completed the study (50 in the salmon calcitonin nasal spray group and 41 in the other group). Lumbar BMD increased significantly in the salmon calcitonin group from baseline (3.0%, p=0.005) and in comparison to the non-calcitonin-treated group (p=0.009). The salmon calcitonin group also had a significant increase in femoral neck BMD compared with baseline values (3.1%, p=0.0005) and in comparison to the non-calcitonin-treated group (p=0.0005) in Ward's triangle BMD (2.9% from baseline values, p=0.009) and in comparison to the non-calcitonin-treated group (p=0.005) in trochanteric BMD (3.4% from baseline values, p=0.007) and in comparison to the non-calcitonin-treated group (P=0.01). Urinary Ca/creatinine and Pyrilinks-D/creatinine levels were significantly decreased from baseline in the salmon calcitonin-treated group (-6.1 and -6.3%, respectively, p=0.001). Bone-specific alkaline phosphatase levels were also significantly decreased from baseline in the salmon calcitonin-treated group (-3.6%, p=0.003). In the same group, a significant decrease in iPTH serum levels compared to baseline values (-2.5%, p=0.005) and in comparison to the non-calcitonin-treated group (p=0.005) was noted. In conclusion, in this pilot study, 1-year intermittent treatment with 200 IU intranasal salmon calcitonin and low doses of 1alpha(OH)D3 produced a significant effect on bone turnover and BMD in postmenopausal women with osteoporosis.

A randomized trial of nasal spray salmon calcitonin in men with idiopathic osteoporosis: effects on bone mineral density and bone markers.

In a 12-month randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover. Twenty-eight men with idiopathic osteoporosis aged 27-74 years (mean, 52.4 years) were randomized to receive either nasal SCT (200 IU) or a nasal placebo daily for a period of 1 year. All the men received a daily supplement of 0.5 g of calcium. The men who received SCT had a mean (+/-SEM) increase in BMD of 7.1 +/- 1.7% at the lumbar spine. In contrast, the men who received the placebo had an increase of 2.4 +/- 1.5% (p > 0.05) for the comparison with baseline. The increase in lumbar BMD in the calcitonin group was significantly greater than that in the placebo group (p < 0.05). There were no significant changes in the femoral neck, trochanter, or Ward's triangle relative to both baseline and placebo after 12 months. Treatment with nasal SCT resulted in a significantly pronounced suppression of bone resorption markers (urinary deoxypyridinoline [DPD], type I cross-linked N-telopeptide [NTX], and type I cross-linked C-telopeptide [CTX]) and to a lesser extent in bone formation markers (serum bone-specific alkaline phosphatase [BALP], osteocalcin [OC], serum C-terminal procollagen type I extension peptides [PICP], and serum N-termnal procollagen type I extension peptides [PINP]), whereas the placebo did not. Therapy was tolerated well and there were no treatment-related adverse events. We conclude that intranasal SCT (200 IU daily) is safe and effective in increasing lumbar BMD and reducing bone turnover in men with idiopathic osteoporosis.

The effect of short-term calcitonin administration on biochemical bone markers in patients with acute immobilization following hip fracture.

The effect of salmon calcitonin on changes in mineral metabolism was studied in 40 elderly patients with recent hip fracture. All patients underwent surgery (internal fixation) 1 week after admission and were randomly divided into two equal groups: group A, which received no treatment, and group B, which received 100 IU/day salmon calcitonin intramuscularly for 2 weeks starting on admission. Blood and 24-h urine parameters of mineral metabolism were measured on admission and at the end of weeks 1 and 2. No intra- or intergroup changes in serum calcium, phosphorus or alkaline phosphatase were observed. At the end of week 2 biochemical markers of bone resorption (urinary calcium and hydroxyproline) had significantly increased in group A and significantly decreased in group B, indicating a reduction in bone resorption in group B. Urinary phosphorus had also increased in group B, possibly due to the phosphaturic effect of calcitonin. It is concluded that immobilization resulting from a hip fracture, and possibly surgery itself, causes significant changes in biochemical markers of bone resorption. Calcitonin successfully reverses these changes and may also be effective in preventing subsequent bone loss, particularly in patients who cannot be remobilized immediately.