Short summary

This study is utilizing the Danish social security system, were all citizens have a unique id number from birth to grave. Using this unique id number patients can be traced in several national registries after permission have been obtained the Danish authorities. In order to answer the four previous stated research questions, a study population will be defined as people who since 2012 have been diagnosed or treated for an osteoporotic compression fracture of spine. Please see attached protocol.

Rationale

Background: Osteoporosis is a generalized disease of the skeleton defined by reduced bone mass and strength. This is associated with an increased risk of low-energy fractures. According to WHO, osteoporosis is present if individuals bone mass is 2.5 standard deviations (SD) below the peak bone mass. Based on this definition more than 500,000 Danes over the age of 50 are at present suffering from osteoporosis. Due to the demographic shift with a growing proportion of elderly in the population, there will be an increased number of citizens suffering from osteoporosis. As every third woman and one in eighth males are affected by osteoporosis, this is one of the major public diseases. Further, it is expected that the number of citizens suffering from osteoporosis will increase four-fold within the next 50 years. A significant proportion - approximately 50% - of patients with osteoporosis will experience a fracture of the spine. Unfortunately, a single spine fracture starts a cascade by increasing the risk of subsequent fractures - the risk of an additional fracture is five times increased in a patient with a single fracture and the risk increases more than tenfold with additional osteoporotic fractures. Clinically a vertebral compression fracture causes back pain. The severity of pain following an osteoporotic vertebral compression fracture is variable. Fortunately, the majority of patients are able to continue with their normal activities of daily living within a time span of 2-6 weeks. However, some patients are severely incapacitated requiring hospitalization. Inpatients are frequently treated with pain medication and sometimes with a back brace to facilitate quick mobilization with the aim to reduce the risk of loss of muscle mass, worsening of the osteoporosis and deep vein thrombosis. Vertebral compression fractures not only cause back pain and loss of function, but can also result in a progressive spinal deformity, decreased lung capacity and gastrointestinal dysfunction. Further, some studies have shown a 23 % increase in 1-year mortality. A spinal osteoporotic fracture affects the individuals' quality of life, results in an increased morbidity and mortality and further results in a significant cost for both the patient and society for medication and care. According to the Danish treatment guidelines, all patients with an osteoporotic fracture should be referred to a Dual energy X-ray absorption scan (DXA-scan) to verify the diagnosis. With the aim of reducing the risk of further fractures, both non-pharmacological and pharmacological treatment of osteoporosis is recommended. The non-pharmacological fracture prophylaxis is based on lifestyle interventions in the form of an appropriate diet, increased physical activity, fall prevention, smoking cessation and reduction of alcohol consumption. Pharmacological treatment consistent of drugs used to treat osteoporosis. Traditionally they are divided into antiresorptive drugs inhibiting osteoclast activity and bone anabolic agents. In patient cases were mobilization is prevented due to severe pain, vertebroplasty has been suggested as a treatment option. This is a minimal invasive, X-ray-guided operation in which needles are placed in one or both pedicles, after which bone cement is injected into the collapsed vertebra. Currently there is no overall overview of the patient flow in the secondary sector in Denmark of patients with osteoporotic spinal fractures, the need for auxiliary measures for this group of patients, the societal and individual costs or the social impact after a spinal fracture.

Purpose: • Establish an overview of the number of primary contacts in the secondary sector due to osteoporotic compression fractures in the spine, including the number of hospitalizations and hospitalization time. • Establish an overview of the direct treatment costs of diagnosing, treating and rehabilitating patients with compression fractures. • Establish an overview of consequences for labor market affiliation and absence. • Establish the mortality and morbidity rate in patients with osteoporotic vertebral compression fractures undergoing vertebral augmentation versus non-surgical management.

Description of the cohort

Identification of study population: The project's study population is defined as people who since 2012 have been diagnosed or treated for an osteoporotic compression fracture of spine at the Spine Center in Middelfart.

Data and biological material

From inspection in the National Patient Register (LPR) for a corresponding period (possibly a few years earlier), an LPR-identified population is identified on the basis of registered diagnosis and treatment codes. This patient population is identified by social security number, date of first osteoporotic diagnosis and first initiated treatment, as well as specified categorization of osteoporosis diagnosis and initiated treatment. It is possible that the study period for the sub-populations may be extended to include previous years. For an incidence analysis, it may be relevant, for example, to include a "wash-out" period, in which prevalent cases are excluded.

From the Danish Medicines Register, persons are identified who during the period have received osteoporosis-related medicines from the primary sector. The inclusion criteria must be further specified in relation to relevant drug groups and requirements for repeated dispensations within a limited period - eg a minimum of 2-3 dispensations within a 6-month period. A wash-out period is also used for this population.

From the surgical spine database DaneSpine, where it is expected that around 1000 patients have been registered at the Spine Center in Middelfart. After approval by DaneSpine board, the same withdrawal criteria are used for patients in the rest of the country. In addition, there will be a number of descriptive variables that are only registered in DaneSpine - including health-related quality of life reported by generic instruments such as EQ-5D and SF-36, as well as a number of disease-specific instruments. There are expected to be cases where the same person is identified in both the DaneSpine, LPR, and drug registry populations. This is to be expected and will be the focus of a closer analysis.

Finally, based on the CPR register, an age, gender and municipality of residence matched control population with 5 controls per identified study case is identified. It must be ensured that there is no overlap between the control population and the LPR-identified population. For individuals found in either the LPR or drug registry group and the control population, the person is removed from the control population. The study population thus consists of the common set of the different subpopulations, which are identified on the basis of different data sources.