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The prevalence of primary hyperparathyroidism (HPT) varies between 1 and 4/1.000 in the general population. HPT is nowadays most often asymptomatic. The classical bone disease has been replaced by osteopenia or osteoporosis with a preferential bone loss in cortical sites. The incidence of nephrolithiasis has been considerably lowered, but renal lithiasis is still the most frequent complication of HPT. The diagnosis is most often made by chance or during the workup of an abnormal bone mass. Hypercalcemia and an elevated PTH concentration, or at least a PTH level in the upper part of the normal range, generally point to a diagnosis of HPT. Additional tests include an evaluation of renal function, vitamin D measurement, determination of 24-hour urinary calcium and bone densitometry. Besides symptomatic HPT, classical recommendations for surgery include age less than 50, serum Ca at least 1 mg/dl above the upper limit of normal, creatinine clearance < 60 ml/min and osteoporosis. Surgical referral will, however, take into account patient age and comorbidities, as well as patient preferences. In the hands of an experienced surgeon, the success rate of parathyroidectomy is 95-98% and the rate of permanent complications is 1-3%. Parathyroid scintigraphy is the best preoperative localization technique of the adenoma. When surgery is contraindicated or refused by the patient, bisphosphonates or cinacalcet can be indicated in cases of osteoporosis or clinically significant hypercalcemia, respectively.

Osteoporosis is a major public health problem. For the time being, the diagnosis of osteoporosis relies on densitometry (T-score < -2.5 by DXA), although the risk of fracture depends also on other factors than the bone mass. Osteoporosis diagnosis (DXA) must be distinguished from the individual risk assessment of fracture. Different risk factors complementary to bone mass have been already validated in different populations. These include an old age, a history of fracture after the age of 50, a familial history of hip fracture (father or mother), a low BMI (< 20), corticoid treatment (> 3 months), tabagism and excessive alcohol consumption. A WHO taskforce has combined these different factors in order to integrate them in a 10-years predictive risk model of fracture (FRAX**). This model should still be validated in different populations, especially in populations not included in its development, which is the case for Belgium. We are evaluating these different risk factors for fracture in a Brussels population of 5000 women (60-80 years) who will be followed each year during 10 years. We also assess the predictive value of other risk factors for fracture not included in the WHO model (tendency to fall, use of sleeping pills, early non substituted menopause, sedentarity, ...). In an interim analysis of the first 452 women included and with data yet available at the time of this writing, we could find a significant (P < 0.05) relationship between diagnosis of osteoporosis at DXA and the number of risk factors, age > 70 years, a personal history of fracture after 50 years and a BMI < 20.

The most frequent sites of osteoporotic fractures are the vertebrae, the hip, the forearm and the proximal humerus. Drugs that inhibit bone resorption constitute the mainstay for the treatment of postmenopausal osteoporosis. A recent meta-analysis indicates that vitamin D can reduce the risk of hip fractures only if calcium supplements are also administered. The effect of hormone replacement therapy on the risk of non vertebral fractures is less clear than on vertebral fractures. Raloxifene (a SERM) reduces the rate of vertebral fractures and of breast cancer, but it does not protect against hip fracture. Bisphosphonates are the most commonly used compounds to treat postmenopausal osteoporosis. The level of evidence for currently used bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) to reduce vertebral fracture rate is maximal. Results of controlled clinical trials indicate a reduction in the risk of vertebral fractures of 40-50% and of 20-40% for non vertebral fractures, including hip fractures. However, their relative efficacy on hip fractures has been less well studied and remains more controversial. Long-term compliance of bisphosphonate therapy is improved by intermittent schemes. The most recent developpements concern the intravenous administration of ibandronate and even more of zoledronate (yearly infusions). The reduction in the rate of vertebral and hip fractures has been demonstrated in the main zoledronate trial and a prolongation of survival has been shown in the study including patients with a recent hip fracture. Whereas hyperparathyroidism is a cause of bone loss, the intermittent administration of parathyroid hormone or of its 1-34 fragment (teriparatide) exerts anabolic effects on the skeleton. The treatment is demanding and costly (daily sc injections during 18 months), requires some monitoring (serum and urinary calcium) but the results, at least for vertebral fractures, are quite favorable. Strontium ranelate is a less powerful stimulator of bone formation but it also reduces bone resorption. Its daily administration for 3 years reduces the risk of vertebral fractures and, to a lesser extent, of non vertebral fractures. Lastly, denosumab is a high affinity antibody against RANK Ligand that specifically blocks the formation and the activity of osteoclasts. The efficacy of this promising compound will soon be known.

Bone pain and bone deformities are the most common manifestations of Paget's disease of bone, even if the diagnosis is nowadays most often made by chance following a routine measurement of serum alkaline phosphatase. Woven bone is formed following a marked increase in bone resorption due to a stimulation of osteoclast activity. Biphosphonates constitute the modern treatment of Paget's disease of bone. Tiludronate (Skelid), or better risedronate (Actonel), are administered orally every day during at least 2 months. Zoledronic acid (Aclasta), as a single 15-min 5 mg infusion, has been recently compared to risedronate, 30 mg/d orally for 2 months, in two randomized studies including 357 patients. Zoledronic acid had a superior therapeutic efficacy, as judged by its rapidity of action, the duration of the biochemical response and the percentage of responders. Thus, at 6 months, alkaline phosphatase levels were normalized in 89% of the patients in the zoledronic acid group as compared to 58% in the risedronate group. The most frequent side effect was a flu-like syndrome, observed in 10% of the patients. An adequate intake of calcium and vitamin D is recommended to avoid posttreatment hypocalcemia. The introduction of Aclasta should simplify and improve the therapeutic management of Paget's disease of bone.

Gabapentin (GBP) is a new antiepileptic agent with an original spectrum of activity. Its mechanism of action has not yet been fully elucidated but appears not to involve binding to GABA receptors despite being a structural analogue of GABA and is distinct from tricyclic antidepressants (TCAs). It has been shown to modulate high threshold calcium currents in brain neurons. As some other anticonvulsants, GBP has been recently proposed for the treatment of noncancer neuropathic pain like diabetic neuropathy and post herpetic neuralgia (double blind studies with placebo). We prospectively followed 20 cancer patients with advanced disease suffering from neuropathic pain. All were already treated for their pain syndrome. We started with 300 mg of GBP given orally in order to reach a dose of 900 mg on D3. All coanalgesics were stopped before entering the study. The only relevant side effect due to GBP was somnolence, otherwise time limited. GBP treatment was associated with a decrease of opioids doses in 9 patients and a decrease of VAS for pain intensity in all cases. Furthermore, the need of rescue doses decreased in all cases but 2. GBP appears to be one of the most effective drugs for the treatment of neuropathic pain. It is well tolerated and its effectiveness appears shortly after its administration. A synergistic action with opioids is suggested. Despite the small number of patients, our study suggests that GBP could be a treatment of neuropathic pain in cancer. Comparative trials should be performed with other neuropathic pain drugs including TCAs and antiepileptic drugs, especially carbamazepine.

We give an overview of the available medical solutions to help a patient with refractory symptoms at the end of his life. Patient "competence" must first be evaluated and, even if their diagnosis is difficult, organic mental disorders and depression must be diagnosed and adequately treated to allow a real, personal and honest dialog. Administration of high doses of morphine is frequently used at the end of life not only to fully relieve pain but also to accelerate death, even if this is not clearly stated. This technique is not devoid of hypocrisy and high doses of morphine can have quite unpleasant side effects. Treatment withdrawal or withholding is generally not sufficient to allow a correct end of life. The arrest of ventilation, dialysis, artificial nutrition and even more hydration must often be coupled with techniques inducing unconsciousness, which makes imprecise the limits between such a "passive" ending of life and "active" euthanasia. The technique of terminal sedation, frequently based on the use of midazolam, has been more recently introduced in some palliative care units. Such a "controlled sedation" is supposed to allow a "natural" death by inducing a profound sleep. In opposition with active euthanasia, which allows a quiet and rapid death at a moment chosen by the patient himself, this technique of "sedation" has an undetermined duration, has legal implications which could be viewed as quite similar as the ones of euthanasia, and, moreover, this prolonged agony can be extremely stressful and distressing for the family. Medical-assisted suicide is allowed in The Netherlands under the same conditions as euthanasia. Death is generally obtained after a few hours but the technique is not always successful and the process of death can sometimes be prolonged and uncomfortable. This technique can nevertheless be preferred by some physicians and patients. As compared to active euthanasia, the proportion of medically-assisted suicides (1/6) is low in The Netherlands. Euthanasia is the only technique able to induce a peaceful and rapid death. The proportion of various techniques to actively induce death is probably quite similar in our country than in The Netherlands but, most of the time, these interventions occur at the very end of life when the patient is no longer able to participate in the decision process and thus occur without his explicit request. We think that, as for all medical decisions, the use of one or the other of these various techniques should be selected after a quiet and free discussion between the patient and his physician, preferably in advance and not in a situation of emergency and panic.

The prevention of osteoporotic fractures in post-menopausal women must be viewed in the framework of the treatment of menopause. SERMs ("Selective Estrogen Receptor Modulators") derivative from steroid hormones have estrogenic and antiestrogenic properties according to the substance and the target tissue. Raloxifene is a second generation SERM. It increases bone mass by 1 to 3% according to the measured site and, after 3 years of therapy at the dose of 60 mg per day, it reduces the incidence of vertebral fractures by 30 to 50% if patients have or do not have vertebral fractures before therapy. This drug is approved for the prevention of vertebral fractures in post-menopausal women at increased risk of fractures. A significant reduction in the incidence of hip fractures has not been demonstrated. Raloxifene exerts favorable effects on cardiovascular risk factors but one has to wait for the results of controlled prospective trials before concluding that raloxifene reduces the risk of atherogeniec disease. Preliminary results indicate a substantial reduction of the risk of invasive breast cancer, still to be confirmed. The incidence of vaginal bleeding does not differ from placebo as raloxifene does not stimulate endometrial proliferation. The most serious adverse event, although infrequent, consists in an increase of the relative risk of thromboembolic disease by 3.1 as compared to placebo. Longer term studies are necessary to compare raloxifene with the estrogen replacement therapy and to determine the extra-bone effects.

The anorexia-cachexia syndrome is a particularly frequent complication of advanced cancer. Parenteral nutrition must remain the exception in palliative medicine but enteral nutrition through feeding tubes or by a gastrostomy is an efficient method to provide an adequate long term nutritional support at home which can improve the quality of life of the palliative care patient. One must never forget all simple means to improve nutritional status. Since the cost benefit ratio of the medications stimulating the appetite, such as the corticosteroids and the progestatives, must still be demonstrated in palliative medicine. Hiccups therapy is essentially based on several non pharmacological means and on the administration of metoclopramide, antacids, haloperidol or chlorpromazine. Chronic nausea is an extremely frequent problem in palliative care, treated most often by metoclopramide, haloperidol and corticosteroids. Constipation is another extremely frequent problem which can lead to serious complication if left untreated. Besides general means, therapeutic means essentially comprise drugs such as lactulose and macrogol, bisacodyl, docusan and prokinetic agents like cipraside.

Supportive care is defined as the totality of medical, nursing, psychosocial and rehabilitative support from the onset of the disease until possible fatal outcome, including all active therapeutic phases. This concept is thus quite large and heterogeneous. The term palliative care is reserved for the approach to the terminal patient. Hospital "Palliative Medicine" should be considered as a subspecialty of Internal Medicine and Medical Oncology. In palliative medicine, symptom control, and no longer prolongation of survival, takes a preponderant place to finally become the only goal to reach. In our mind, a Palliative Care Unit is not necessarily the final stay of a patient where spiritual support will be preponderant. One of our essential goals is always that the patient can come back in his family in collaboration with the family doctor, even for a short time. The ideal situation consists in short stays in the Unit to treat an acute complication before the patient is sent back home or to his Residency. Along this line, a very close collaboration with the family doctor is absolutely essential.

Opioid analgesics are widely acknowledged as the most important drugs for the treatment of chronic cancer pain. Although these drugs can in most cases control severe pain, even when they are used appropriately, they may produce new symptoms or exacerbate preexisting symptoms, most notably nausea and somnolence. The combination of severe pain, anorexia, chronic nausea, asthenia, and somnolence is a frequent finding in patient with advanced cancer. An adjuvant drug should meet at least one of the following criteria: 1) to increase the analgesic effect of opioids; 2) to decrease their toxicity; 3) to improve others symptoms associated with terminal cancer. Many drugs, such as nonsteroidal antiinflammatory agents, tricyclic antidepressants, corticosteroids, benzodiazepines, amphetamines, antiemetics, oral local anesthetics and bisphosphonates have been suggested to have adjuvant analgesic effects. Unfortunately, most of the evidence for the effects of these drugs is anedoctal. Controlled clinical trials are badly needed to precise the indications and the risk/benefit ratios of these agents, some of which have significant toxicity and could potentially aggravate narcotics toxicity.

Patients with advanced cancer frequently present with chronic nausea, emesis, bowel obstruction, confusional syndromes or dysphagia. All these conditions make it difficult for the patient to take oral medications or to maintain an adequate level of hydration by mouth. Hypodermoclysis is a safe and simple method that allows for cost-effective sucutaneous delivery of fluids and drugs. Hypodermoclysis has some clearcut advantages over the i.v. route. It can be started without need for a physician or a nurse, does not immobilize a limb, can be stopped and restarted at any moment without concern for clotting, and its use sparses nursing time. It also allows for easier and safer home discharge. Potentiel side effects of hypodermoclysis include pain at infusion site, sloughing tissues as a result of insufficient fluid absorption, infection, and puncture of vessels with bleeding. This paper gives some guidelines for the use of hypodermoclysis for fluid, electrolytes and drugs frequently used in a palliative care setting. The controversy surrounding the treatment of dehydration in the terminally ili is also briefly examined.

The risk of osteoporotic fractures is currently easily assessed by densitometry. The entities "osteopenia" and "osteoporosis" are less and less separated and, along the same line, it becomes somewhat arbitrary to separate "prevention" and "treatment" of osteoporosis when low bone mass has been diagnosed. An adequate calcium intake is most important in childhood and adolescence, pregnancy and lactation, and in the older population which, moreover, often suffers from vitamin D deficiency leading to cortical bone loss. Supplements of calcium and vitamin D to institutionalized elderly people could reduce by more than one third the risk of hip fractures. Estrogen replacement therapy remains the best means to prevent postmenopausal bone loss; too few women are treated but replacement therapy must be given for at least 7 years to keep a significant residual effect in the old age. Calcitonin has a proved analgesic effect for painful crush fractures and its long term administration can prevent postmenopausal trabecular bone loss. Nasal calcitonin considerably improves treatment tolerance and compliance but its price remains prohibitive. Etidronate is the only oral bisphosphonate available in Belgium. It can increase bone mass but its therapeutic index is too narrow and its antifracture efficacy has not been satisfactorily demonstrated. Pamidronate is a second generation bisphosphonate which has a much better therapeutic index but its usefulness is limited by the absence of an oral formulation. The introduction of third generation compounds will improve the therapeutic approach of osteoporosis if adequate therapeutic schemes are used. Much progress is also awaited concerning stimulators of osteoblastic activity.(ABSTRACT TRUNCATED AT 250 WORDS)