Volume 2 · Nº 3 Supl · July 2010
Osteoporosis is a global health problem whose importance is going to increase with the aging of the population. It is defined as a systemic disorder of the skeleton characterised by low bone mass and deterioration of the microarchitecture of the bone tissue, with the consequent increase in bone fragility and the greater susceptibility to fractures1. Bone resistance reflects essentially the combination of bone density and bone quality. In turn, the concept of bone quality seeks to integrate all those factors apart from bone mass which determine bone fragility, including the microarchitecture, the degree of turnover, the accumulation of lesions or microfractures, or the degree of mineralisation1,2.
It is a process which is preventable and treatable, but which lacks warning signs prior to the appearance of fractures, leading to the fact of few patients being diagnosed at early stages and treated effectively. Therefore, in some studies it has been confirmed that 95% of patients who presented with a fracture did not have an earlier diagnosis of osteoporosis3.
In 1994 the World Health Organisation (WHO) established some definitions based on measurements of bone mass in the lumbar spine, hip or forearm of white postmenopausal women4. Thus, normal bone mass is considered to be having a bone mineral density (BMD) value higher than -1 standard deviation (SD) in relation to the average for young adults (T-score >-1); osteopenia, having BMD values between -1 and -2.5 SD (T-score between -1 and -2.5); osteoporosis, having BMD values lower than -2.5 SD (T-score lower than -2.5), and osteoporosis is established when, along with the above conditions, are associated one or more fragility fractures (Table 1). It is also possible to consider the Z-score in groups of patients such as children and young adults, which expresses the bone mass in comparison with that expected in those of equal age and sex5.
Osteoporosis (OP) is included in the group of diseases which constitute the greatest health problems in the world, both for its ubiquity and for its socioeconomic consequences. In the United States of America it has been calculated that around 10 million people have OP and that nearly 34 million are at risk of suffering a fracture due to their having low bone mass1. In Spain, it is estimated that 3 million people suffer from OP and that this would mean an incidence of hip fracture of approximately 6.94 ± 0.44 per 1,000 inhabitants per year2. However, it is difficult to know exactly the global reach of OP since only data on femoral fractures is known with any exactitude, because it is the only one which always requires hospitalisation. In fact it would be possible to divide the consequences of OP into three well differentiated types of fracture: vertebral fracture (VF), femoral fracture (FF) and non-vertebral, non-hip fracture (NVF). VF has the inconvenience that it is only symptomatic in 30% of cases, and despite a third of vertebral fractures requiring specific medical attention, the rest are underestimated and remain diagnosed as back pain or arthritic lumbago3. FFs are the only truly quantifiable of these fractures, since they always require hospitalisation, at least in countries described as developed, and their costs can be assessed with greater accuracy. NVFs, which would include fractures of the forearm, humerus, clavicle, ribs, and ankle, are also very difficult to quantify, since although some cases require surgical intervention, the majority are attended to in outpatients or casualty departments of hospitals without the patient being admitted.read more
At a time when we have advanced enormously in the knowledge of the natural history of osteoporosis and of the drugs which we use in its treatment, it is necessary to identify those patients at greatest risk in order to focus on them diagnostic therapeutic resources before the final complication, the fracture, appears. This is especially important in the context of finite resources which should be located in the population which would most benefit from them. It is the case, also, that we now know more about the potential risks and limitations of some treatments – for example, the powerful anti-catabolics about which we lack data on their safety beyond 10 years of treatment, or the anabolics, which are considered to be indicated for a maximum of two years – for which reason we need to know at what moment in the natural history of the disease the global risk to the patient is sufficiently important to initiate appropriate treatment.read more
The treatment of osteoporosis in postmenopausal women consists initially of a series of non-pharmacological measures which can be applied to all patients, such as increasing where possible physical exercise, especially that which applies load, a balanced diet with sufficient calcium and vitamin D, exposure to sun for 10 minutes a day at a time when is it less strong, in addition to suppressing smoking and preventing falls1,2. However, in postmenopausal women with osteoporosis, or at high risk of developing it, to these should be added pharmacological measures.
Chronologically, the first drugs developed for the treatment of osteoporosis were the antiresorptives, among which were the oestrogens3-6, calcitonin7 and the first biphosphonates, such as etidronate8,9. All these drugs had a plausible physiopathological basis, and were the confirmation that osteoporosis produces an increase in bone resorption, checked both by the biochemical markers for bone remodelling and by bone biopsies10. Studies carried out with these drugs, as later with other antiresorptive drugs, confirmed that they produced a small increase in bone mineral density which was not related to a reduction in risk of fracture11.
In the last few years a series of drugs have been developed whose action mechanism is based on the direct stimulation of bone formation, and which, together, are called anabolic bone therapies. The objective which all these treatments pursue is the formation of new bone, the restoration of bone microarchitecture, to increase bone mineral density, and thus reduce the risk of fracture. Among these compounds are included fluorine, growth hormone (GH), insulin-related growth hormone type 1 (IGF-1), the statins, and above all, two agents which show the greatest evidence of efficacy: strontium ranelate and parathyroid hormone (PTH) and its active fragments. We focus our review on the whole molecule of PTH, known also as PTH 1-84.