Management Of Osteoporotic Fractures With Biphophonates

Antonio Jiménez Martín, Rosalía Martínez Pérez*, José Luis Marenco de la Fuente*, José Lara Bullón.

Orthopaedic and Trauma Surgery Service. Valme University Hospital. Seville. Spain.
*Rheumatology Service. Valme University Hospital. Seville. Spain. 

Abstract:

INTRODUCTION AND OBJECTIVES: In 2006, 7.2 osteoporotic pelvic fractures /1000 Spanish inhabitants were reported, with only 18% of these being previously treated patients. Our objective was to study the incidence of osteoporotic fractures in our area, recognise the associated risk factors and analyse therapeutic changes taken by us with regards to this growing disease.
MATHERIAL AND METHODS: A retrospective descriptive study, in which we analysed 1432 patients. Average age: 71.50 years, standard desviation: 9.64 years. 98% women. We analysed risk factors for osteoporotic fractures described by Jódar-Gimeno, presence of concomitant pathology, differential diagnoses, treatment before and after the first consultation. The study took place over three years, with an average follow-up of 1 year.
RESULTS: 33.9% referred to a reduced stature, 26.1% described poor visual capacity, 41.8% presented difficulty in getting up out of chairs, 4.6% were treated with  benzodiazepines, 16.8% suffered from vertebral fractures, 21.2% from pelvic fractures, 62.4% suffered fractures in other locations, such as humerus or wrist, 28% suffered from hypertension. They went from a sedentary life (53.6%) to an active life (96.2%) and we achieved a treatment of 72.6% of the cases as opposed to 5.7% previously, with significant statistical differences, p<0.05.
CONCLUSIONS: Cranney observed a statistically significant (p<0.01) reduction of risk of fracture for the hip or wrist, with alendronate. Delmas observed a reduction of 43% of risk of fracture of the hip after 12 months with risedronate, as compared with alendronate. Skedros recognised that for some orthopaedic surgeons, osteoporosis is not a priority, although for Herrera medical awareness of the problem has brought about an increase in diagnosis from 8% to 52% and therapeutic indices of 72.5%.  

J.Orthopaedics 2009;6(2)e13

Keywords:

osteoporosis;fracture; biphosphonates.

Introduction:

Osteoporosis is a progressive disease. Thus, at world level, 126 million hip fractures  were reported in 1990 and 2.6 million are predicted for 2025 and 4.5 million for 2050¹. In Spain, up to 7.2 fractures per 1000 inhabitants have been reported, and only 18% of these patients with fractures have received treatment for their osteoporosis previously to their fracture².

As Farahmand³ has recognised, the significance of osteoporosis is notable, as people in Europe annually suffer from more than 400,000 hip fractures and it is predicted that by 2020 this will have increased to 650,000. On the other hand, a woman of 50 years old, has a more than 50% probability of suffering from at least one fracture due to osteoporosis, with a related risk of death, adjusted for age and hospitalization of 2.3 points (95% CI 2.0-2.5).

Age is a multiplying factor for the risk of osteoporotic fracture. Thus in the study published in  REEMO in 2005⁴, it was recognised that hip fractures supposed a risk of 0.2% appearing at 50 years old, and that this risk multiplied up to 5.2% after 80 years old. In a similar manner, fractures of the wrist can be seen to increase in frequency by up to 2% at the age of 80, with 4.7% of vertebral fractures equally in this age range. All this is associated with the lower bone mineral density of the osteoporotic bone.  Thus the fact of suffering a hip fracture multiplies the possibility of suffering another contralateral hip fracture by 2 times; it multiplies the risk of suffering from a vertebral fracture by 4 times, and the risk of suffering from a Colles⁵ fracture by 2 times. For Millar, 33% of patients with a hip fracture have suffered previous osteoporotic fractures⁶. (Figures 1 and 2).

Figure 1. Subcapital osteoporotic fracture. A hip fracture doubles the possibilities of suffering from another contralateral hip fracture.

Figure 2. Osteoporotic vertebral fracture . Observe the anterior wedging typical of these fractures. This doubles the probabilities of suffering a hip fracture, quadruples suffering another vertebral fracture and doubles suffering a Colles fracture.

Due to the current importance of this disease in general population, it is not justifiable to think that treatment of these fractures should be only surgical or orthopaedic, without considering preventative treatment for osteoporosis, neither should we forget preventative treatment for osteoporosis in menopausal patients. All this led us to suggest the following objectives for this work.

Objectives:

Our objective was to evaluate the incidence of osteoporotic fractures entering the emergency department of the Nuestra Señora de Valme University Hospital of Seville, to evaluate the risk factors most frequently associated with these patients and to revise the types of treatment indicated.

Materials and Methods:

Descriptive, retrospective study, carried out in the Emergency Trauma department of the Nuestra Señora de Valme University Hospital, over a period of 3 years. Follow-up of 1 year per patient.

Our protocol for data collection was centred on the following points:

• Personal details: First name, Surname, age, height, weight, patient number and address/telephone number.

• Risk factors: Weight less than 57 Kg, type of fracture, associated pain, sedentary life style, smoker, maternal history of pelvic fracture, reduced height since 25 years of age, poor eyesight, difficulty in getting up out of chairs, use of anti-seizure drugs, steroids, immune suppressors, benzodiazepines, psychotrophics, thyroid treatment, prior hyperthyroidism, consumption of alcohol, caffeine, early menopause and prolonged amenorrhoea.

• Previous treatment.

• Confirmation of the fracture, clinical or X-ray.

• Differential diagnosis with skeletal tumours, endocrine diseases with bone repercussions, systemic inflammatory diseases or radio or chemotherapy treatment.

• Concomitant pathologies: metabolic, genitourinary, digestive…

• Type of treatment indicated on discharge.

An analysis of the data was carried out by means of the computer program SSPS.

Results :

1432 patients were involved in the study. Their average age was 71.50 years, with a standard deviation of 9.64 years. We observed a minimum of 42 years (early menopause due to hysterectomy and double anexectomy at 31 years) and a maximum of 106 years. 1404 women were observed (98%) and 28 men (2%.)

The most frequent age ranges were those located between 66 and 80 years old, with 242 patients being between 66 and 70 years old, 287 patients between 71 and 75 years old and 237 patients between 76 and 80 years old.

With regards to the risk factors collected for the appearance of osteoporotic fractures according to Jódar-Gimeno⁴ the following stand out: 767 patients state that their usual type of lifestyle before the trauma was sedentary (53.6%), 485 patients referred to a reduction in height (33.9%), 11 patients presented suppressed immune system (0.8%), 374 patients referred to poor eyesight (26.1%), 599 patients referred to difficulty getting up out of chairs (41.8%), 16 patients took anti-seizure drugs (1.1%), 66 patients took benzodiazepines (4.6 %), 8 patients had no risk factor (0.6%) and 82 cases (5.7 %) presented a weight of less than 57 kg.

Diverse fractures were reported. Thus, 241 cases of vertebral fractures, that is to say, 16.8 % of the patients presented some type of vertebral fracture. 304 cases of hip fractures, (21.2 % of the total), 894 cases of non-vertebral fractures, excluding hip fractures, (62.4 %) and 1210 patients referred to pain associated with the fracture, 84.5% of the whole serie. The remainders did not state pain as the principal symptom, which sometimes caused an under diagnosis. 818 cases, 57.1%, were clinically   confirmed, as opposed to 51 cases, 3.6 %, which were confirmed by X-ray.

With regards to associated pathologies, we observed that 5 patients had bone tumours or other neoplasies (0.3%), 4 patients had endocrine diseases that affected bone metabolism, such as hyperthyroidism (0.3%), 1 case of Paget’s disease (0.1 %), no cases of ankylosing spondylitis, systemic lupus erythematosus or treatment with chemo/radio therapy, arterial hypertension in 401 cases (28%), no case of inexplicable uterine bleeding, 1 case of benign mammary pathology (0.1%), no case of endometriosis or severe renal insufficiency, 5 cases of renal  lithiasis, (0.3%), 3 cases of active oesophageal disease of the gastro-oesophageal reflux disease type (0.2%), 5 cases of cholestasis (0.3%), 5 cases of cholelithiasis (0.3%), 2 cases of intense  migraine (0.1%), 1 case of chronic rhinitis (0.1%), 3 cases of confirmed hot flashes (0.2%), 181 cases of diabetes (12.6%), 94 cases of hyperlipaemia (6.6 %), 2 cases of endometrial cancer (0.1%), no uterine leiomyoma, 4 cases of breast cancer (0.3%), no case of venous thrombosis or pulmonary thromboembolism and 5 cases of evident interphalangeal arthrosic nodules (0.3%).

The treatments at the start of the study were the following: Alendronate in 50 patients (3.5%), calcitonin in 0 patients, etidronate in 0 patients, raloxifene in 6 patients (0.4%), risedronate in 32 patients (2.2 %), calcium and vitamin D in 42 patients (2.9 %), PTH in 0 patients, strontium ranelate in 0 patients and alendronate associated with cholecalciferol in 0 patients.

The treatments after discharge were the following: 650 patients were treated with calcium and vitamin D (45.4%), 1378 patients led an active lifestyle following advice from their doctor (96.2%), 709 patients expressed their intention to avoid smoking and alcohol (50.9%), 1428 patients followed a healthy diet with dairy products (99.7 %), 976 patients were treated with alendronate (68.4%), 7.85 % of the patients were treated with alendronate and vitamin D, 60 patients were treated with risedronate (4.2 %), 0 patients were treated with etidronate, 8 patients with raloxifene (0.6%) and finally, 0 were treated with strontium ranelate or PTH.

47.22% were treated with osteoactive and vitamin D supplement and 49.14% of the patients with osteoactive only. 90.44% of the patients did not have any treatment before fracture, but treatment with biphophonates was iniciated. Only 0.78% of the cases received with initiated treatment left with none, which indicates the high percentage of patients for whom treatment was initiated. All this led to an increased proportion of the patients who participated in this study, going from 21 cases in 2003 to 1432 patients at the start of 2007.

767 patients stated that their normal lifestyle before the trauma was sedentary (53.6%), 1378 patients had an active lifestyle after advice from their doctor (96.2%), which brought statistically significant differences. (p<0.05).

On the other hand, the patients treated with biphosphonates rose from 5.7%  to 72.6%, with a clear statistically significant difference. (p<0.05).

Discussion :

Osteoporosis is a situation of bone fragility that has to be treated, as is recognised in the publications of the American Association of Orthopaedics Surgeons, in which Herrera⁷ describes a multi-centred study of 55 hospitals, including 12742 cases, which demonstrate an increase in the percentage of patients with treatment from 7.5% to 72.5% and an increase in the diagnosis from 8% to 52%.

In this review the treatments employed in our centre were analysed, although there certainly exist diverse treatments for osteoporosis. Thus, the current diverse treatments considered are those such as PTH, which has brought about increases of 7% in the bone mass of the lumbar vertebral column; teriparatide, which has achieved an increase in the bone mass of up to 9.7% in the lumbar column, with a reduction of 65% in vertebral fractures; strontium ranelate, used for lumbar vertebral fractures; arzoxifene, bazedoxifene, MDL 103323, ospemifene, isoflavones…; ibandronate, which supposes increases of 5% in the bone mass of the lumbar column;  zoledronate, with benefits of 5.8% in the lumbar column …etc. For Chesnut⁸, intranasal calcitonin produced an increase in the number of trabeculae, reducing the space between them, thus benefiting bone quality by improving the micro-architecture and increasing the bone volume. It prevents vertebral fractures and has a rapid analgesic action, raising the levels of beta endorphins⁹ and reducing the number of bedridden patients after 4 weeks of treatment, according to Lyritis¹⁰. Other therapeutic agents under study are SB-357114 (inhibitor of cathepsin K), the antagonists of integrin receptors, HCT-1026, osteoprotegerin, CGP-77675, and AP-23588. Nevertheless, biphosphonates are the most used¹¹.

PTH has recently been of interest, as for authors like Silverman¹², synthetic PTH has led to reductions in the risk of vertebral fractures of up to 53% in patients with a prevailing fracture risk and up to 68% in patients without a prevailing vertebral fracture. According to Black¹³, combination of PTH and alendronate has provided an increase in lumbar bone mass of 12% above the increase of 4% reached with PTH and  placebo 24 months after the initiation of treatment.

In our experience, the most used medications have been biphosphonates, and specifically, alendronate and risedronate. However, in this therapeutic field, huge differences have now been found, which can bee seen by looking at the bibliography.

In this regard, there are authors who defend the administration of alendronate. Thus, for example, there is a statistically significant reduction in the risk of hip fracture, using alendronate and risedronate, with p<0.01, however, this reduction is not maintained in the prevention of fractures of the forearm for risedronate, with p=0.29¹⁴. A 63%¹⁵ reduction in the risk of hip fracture has also been found at 18 months in women, with or without previous fractures, when treated with alendronate, with p=0.014 as opposed to a placebo, and a 90%¹⁶ reduction in the risk of multiple vertebral fractures 3 years later in women with previous fractures when treated with alendronate, p>0.001, as opposed to a  placebo, something that is not found with risedronate. For Moroni, the tensile strength necessary to extract osteosynthetic material in patients with hip fractures treated with alendronate is greater than in those patients treated with a placebo, specifically, 2558 ± 1103 N/mm in the group treated with alendronate, as opposed to 1171 ± 480 N/mm in the group without alendronate (p < 0.0005), which leads one to conclude that this biphosphonate improves the quality of the osteosynthesis in bones with osteoporosis¹⁷.

If we consider the meta-analyses, the reducción of the relative risk of fracture according to Cranney is around 50% for alendronate, for both vertebral and non-vertebral fractures¹⁴; for Papapoulos¹⁸, his meta-analysis indicates a reduction in the risk of hip fracture in all the studies of treatment with alendronate in post-menopausal women, with and without previous vertebral fractures, giving evidence of the consistency of the effect of alendronate in the reduction in the risk of hip fracture.  Finally, for Liberman¹⁹, alendronate reduces the risk of hip fracture and non-vertebral fracture by 45-55%, treatment with hormonal substitutes by 25-36% and risedronate by 26-27%. The available evidence about ibandronate, calcitonin, etidronate and raloxifene in these fractures is insufficient and inconsistent.

However, other authors recommend the use of risedronate. Thus, for Silverman and Delmas²⁰, there exists a reduction of 43% of the accumulative incidence of hip fractures with risedronate after 12 months of treatment, when compared with patients treated with alendronate. Roux²¹ highlights the reduction of up to 92% of the relative risk of clinical vertebral fracture, RR=0.08, 95% IC, 0.01-0.63, with the weekly administration of risedronate, and Harrington²² indicates a reduction of 66% in the risk of clinical non-vertebral fracture, 95% IC 4-89%; p=0.048, with risedronate.

Conclusion:

With this study in our centre, identification and treatment of patients with osteoporosis has been improved. It has raised the awareness of the treatment of this pathology in the daily hospital practice. The specialists in Orthopaedic and Trauma Surgery and Rheumatology have to treat the consequences of osteoporosis, the fractures, and their prophylaxis is also in their hands, for which the biphosphonates are an effective instrument.  With this study, we have managed to increase the treatment and prevention of osteoporosis in our centre. Probably, and thanks to the results obtained in our study, we consider that there must be a protocol for treatment with biphosphonates and D vitamin  when these patients go out of hospital.

Reference :

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10. Lyritis GP, Paspati I, Karachalios T, Ioakimidis D, Skarantavos G, Lyritis PG. Pain relief from nasal salmon calcitonin in osteoporotic vertebral crush fractures. A double blind, placebo-controlled clinical study. Acta Orthop Scand Suppl.1997 Oct;275:112-4. 

11. Arboleya LR, Morales A, Fiter J. Effect of alendronate on bone mineral density and incidence of fractures in postmenopausal women with osteoporosis. A meta-analysis of published studies. Med Clin (Barc).2000;114 Suppl 2:79-84. 

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13. Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med.2005 Aug 11;353(6):555-65. 

14. Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C. Meta-analyses of therapies for postmenopausal osteoporosis. IX: Summary of meta-analyses of therapies for postmenopausal osteoporosis.  Endocr Rev.2002 Aug;23(4):570-8. 

15. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al.  Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet.1996 Dec 7;348(9041):1535-41. 

16. Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, et al. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group.  J Clin Endocrinol Metab.2000 Nov;85(11):4118-24. 

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This is a peer reviewed paper 

Please cite as: Antonio Jiménez Martín: Management Of Osteoporotic Fractures With Biphophonates.

J.Orthopaedics 2009;6(2)e13

URL: http://www.jortho.org/2009/6/2/e13

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