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Osteoporosis-associated bone loss is manifested as chronic pain, fractures and reduced quality of life. Osteoporosis increases the risk of fracture, especially in elderly people. Here we present the role of family doctor in osteoporosis management for the prevention of the occurrence of fractures, also particularities of medical and non-medical therapeutics. The preventive aspects and actual therapies plans of the disease are presented as a useful tool for healthcare givers implicated in osteoporosis treatments. In conclusion, family doctors play an important role in the global strategy for the prevention and treatment of osteoporosis and its socio-economic consequences.
Osteoporosis-associated fractures are common1 and the number of people at high risk of fractures is estimated to double globally over the next three decades.2 Osteoporosis consequences have a significant impact on the quality of life, autonomy, and residual disability with increasing costs for treatments.3-5
Osteoporosis was found as the 10th ranked major illness in the United States.6 One in two women and one in five men will experience a fracture in their remaining lifetime from the sixth decade of life. Also, chronic treatment with glucocorticoids, anticoagulants,7 human immunodeficiency virus (HIV) infection8 or HIV/hepatitis C co-infections9 have an increased risk of osteoporosis and fractures. Osteoporosis costs for treatments remain among very expensive expenses for Medicare beneficiaries.6
Practical approaches have been established to prevent fractures, primary and secondary, and many interventions have been investigated to calculate the effectiveness and the adherence to medication.10 There are several effective treatments that ameliorate bone mineral density (BMD) and reduce significantly the risk of fragility fractures. Education programs are important for counselling people about the safety and efficacy of treatments3 also physical moderate exercise. However, a notable global difference between the number of patientswho should be treated for osteoporosis and the number who are treated is reported,11 and between the adherence of the recommended treatments in the general population.12
Worldwide, significant efforts are ongoing,1 e.g. under the auspices of organizations such as the International Osteoporosis Foundation. However, efforts are needed at all levels, including nationally and internationally, to diagnose and to treat all patients at high risk of fracture.2 Usually, the bone loss does not cause symptoms, although individuals have chronic low back pain due to microfractures2 and reduced health-related quality of life. The main signs that appear are height loss, pain, dorsal kyphosis, and fracture symptoms.
The appearance of osteoporotic fractures is usually secondary13 to a trauma or a fall (falling from one's height), but there are situations when the fractures occur spontaneously or as a result of minimal trauma (coughing effort, lifting a weight). Factors that increase the risk of falling are vision and coordination disorders, impaired gait, associated neurological and rheumatic diseases, the use of sedatives.14
The most common fractures are vertebral, distal radius, femoral neck, fist, humerus. Vertebral fractures occur more frequently at the thoracolumbar junction. Vertebral pain caused by an osteoporotic fracture has a deep and diffuse character in the spine, is accentuated by the movements of the trunk, and is relieved at rest.15 The fracture of the distal radius (Colles fracture) is also encountered with a higher frequency and is due to falling with the hand in extension on the forearm.16 The fracture is painful, requires orthopedic reduction and immobilization in a cast for 4-6 weeks. Frequently, patients remain with radius deformity and a degree of functional impotence at this level.17 Hip fractures are the third most typical category of osteoporotic fracture. They occur in late osteoporosis in which there is simultaneous, almost equal loss of trabecular and cortical bone. The consequences are essential: disabilities, high economic costs, high mortality.18
Decreased bone mass is the leading risk factor for osteoporotic fracture. Numerous prospective studies confirm this link. These studies, different in the geographical origin of the cohorts and the densitometric methods used, show an exponential trend in the increasing incidence of fractures that accompany the progressive decrease in bone mass.19 It should be noted that the decrease with a standard deviation (10-15% of bone mass) doubles the risk of osteoporotic fracture, being valid for all measurement sites: spine, femur, calcaneus.20
Current therapeutic aspects
The preventive and current therapies aspects of the disease are targeted. In general, groups of women during menopause are studied, and bone density, fracture risk, and the number of fractures produced in the long bones, especially in the vertebrae, are evaluated.19
Ways to influence this condition are medicinal and non-medicinal. The drug solutions that underlie the therapy of osteoporosis target the agents that influence bone metabolism. They address both processes involved in bone remodeling – bone resorption and synthesis.19 Agents that oppose resorption or that promote synthesis are used. However, their effects are not strictly limited but interfere. Among the medicinal agents that mainly oppose resorption are estrogens, calcitonin, bisphosphonates, vitamin D.21 Drugs that stimulate new bone formation include sodium fluoride, anabolic steroids, vitamin D metabolites, and hormonal combinations containing estrogen, progesterone, androgens – Figure 1.21
Bisphosphonates represent the most used anti-osteoporotic agents. Commonly used bisphosphonates are alendronate, risedronate, ibandronate, and less frequently, zoledronate. The potency of bisphosphonates varies from one compound to another, the oral bioavailability being low.22 They are administered orally or intravenously (i.v.). The main side effects of oral administration are esophagitis and, in the case of i.v. administration, flu-like syndrome. Jaw necrosis, secondary to bisphosphonate administration, is rare, especially after i.v. administration, and for high doses.17 Bisphosphonates are given intermittently (alendronate 70 mg/week; risedronate 35 mg/week or 75 mg on two consecutive days per month; ibandronate 150 mg orally once a month or 3 mg iv once every three months; zoledronate can be used in osteoporosis in 5 mg dose i.v. once a year). The duration of treatment is dictated by the effectiveness of therapy, increased BMD, and reduced risk of fractures; there are studies in which alendronate has been administered for ten years.18
Calcitonin is administered as a nasal spray of 200 u.i./day or intramuscular injections. The increase in BMD is modest, but the administration of calcitonin significantly relieves the pain associated with vertebral fractures.23 It is administered for up to 6 months to prevent the onset of tolerance.24
Estrogen hormones – correction of estrogen deficiency slows down the rate of bone loss in elderly women with osteoporosis or not, regardless of age. Estrogen replacement should be continued for at least 8 to 10 years to maintain favorable effects on bone tissue.2 The preparations used contain estrogen or an estrogen-progesterone combination that reduces the risk of genital bleeding. The results of the WHI study showed an important reduction in the frequency of fractures, but combined with an increased risk of the occurrence of breast cancer and also for cardiovascular events led to the discontinuation of the study, and made osteoporosis a questionable indication for estrogen replacement.25
Selective estrogen receptor modulators (SERMs). Raloxifene is a SERM that acts as an agonist on the bone and an antagonist on the breast and uterus. It is administered orally, 60 mg/day. It increases bone mass, lessens the risk of fractures, reduces the incidence of breast cancer, but has an increased risk of venous thrombosis, exacerbates vasomotor disorders, hot flashes, pulmonary embolism, and brain death. A study that monitored and compared post-marketing use of raloxifene in women aged <75 years versus women ≥75 years showed no difference in the overall adverse events of raloxifene.15
Denosumab belongs to the class of RANK ligand inhibitors, having the effect of decreasing bone resorption by suppressing the maturation of osteoclasts. Calcium and vitamin D levels should be normal before starting treatment. It is administered as a subcutaneous injection of 60 mg every six months. The most common side effects are joint pain and myalgia in the upper and lower limbs, local allergic reactions, and hypocalcemia. The risk of maxillary necrosis is present, as in the case of bisphosphonates. Several antiresorptive pharmaceuticals are being studied, such as cathepsin K inhibitors (odanacatib) and sclerostin inhibitors (romosozumab), with promising results in preventing osteoporotic fractures.26
Drugs that stimulate bone formation
Intermittent administration of parathormone reduces the risk of vertebral and non-vertebral fragility fractures, increasing BMD in the trabecular bone compared to the cortical bone. The dose is 20 micrograms subcutaneously once a day. The treatment is aimed at patients with severe osteoporosis, and the duration of treatment should not exceed two years.
Parathyroid hormone has a significant role in regulating bone metabolism through its direct effect on osteoblasts and indirectly by stimulating the release of growth factors and cytokines to stimulate osteoformation.27
Strontium ranelate supports bone formation and diminishes bone resorption, decreasing vertebral fracture risk23 and hip. It is administered 2 g/day orally, away from meals. In phase III studies, treatment was associated with increasing the annual incidence of venous thromboembolic events.
Combined and sequential treatment
The concomitant use of two antiresorbent agents or one antiresorbent agent (bisphosphonate or SERM) after treatment with parathormone analogs has a favorable effect. Initial administration of bisphosphonates with a strong antiresorbent effect will decrease the effectiveness of subsequent administration of another bisphosphonate, parathormone, denosumab, or strontium ranelate.28
Finally, we should mention the favorable situation, in which due to the calcium retention induced by thiazide diuretics, osteoporosis is delayed in patients taking such drugs.
Symptomatic treatment of bone pain
Symptomatic treatments of bone pain use common painkillers and non-pharmacologic measures.
Non-drug treatment
Non-drug treatment consists of the following general measures: calcium and vitamin D taken from diet.
Some authors emphasize the role of calcium intake in the diet, more favorable than drug supplements. The recommended dose of calcium is 1 g/day. The prophylactic dose of vitamin D is 800 microns/day.21 Synthetic vitamin D analogues are calcitriol and alfacalcidol. Calcitriol (1.25 OH D3) results from the hydroxylation of vitamin D3, initially in position 25 in the liver and later in position 1α in the kidneys. It is important to note that hepatic hydroxylase fulfils its mission even in advanced hepatic impairment.
In contrast, renal hydroxylase is strongly influenced by the existence of renal impairment, which depresses renal hydroxylase and is strongly influenced by its proper functioning. The prescribed doses shall not exceed 0.5 micrograms/day for calcitriol and one microgram/day for alfacalcidol. Calcium, phosphatemia, calcium, and renal function tests will be monitored. The administration of vitamin D in high doses at intervals of weeks, months, or even annually (e.g., 200,000 microns, 400,000 microns, 600,000 microns at a time) will be considered only for non-compliant patients, with higher risks of side effects.
General non-pharmacological measures (Figure 2) are represented by hyposodic diet, constant exercise, avoiding smoking and alcohol abuse that promotes bone loss, avoiding the combination of drugs with bone resorption effect, avoiding falls in elderly patients, removing obstacles and slippery surfaces, performing tonic exercises on the muscles, and administering cerebral vasodilators to prevent falls and consecutive fractures.
"Gap” in the treatment of osteoporosis
In spite of numerous advances in the diagnosis and treatments for osteoporosis and for reduction of risk of fractures, combined with the production of best practices guidelines, many reports indicate that just a minority of population at high risk of fracture receive prescribed treatment.
Surprisingly, less than 20% of patients with fragility fracture receive prophylactic therapies to decrease the risk of subsequent fractures, meagre treatment rates for elderly women, and those hospitalized in long-term care facilities.2
Inconsistencies in the use of fracture risk assessment instruments such as FRAX vary 1000 times worldwide, with much greater variability than the 30-fold range of gross or ten-fold range of age-standardized hip fractures worldwide, indicating a significant gap in service delivery.
Limitations on the internet facilities, the lack of national osteoporosis assessment guidelines in many countries, and the availability of unconventional algorithms may partly be responsible for these differences. Apart from the lack of assessment and treatment of those at very high risk of subsequent fractures, the most worrying concern is the reduced trend of the population treated for hip fracture, demonstrated in both the U.S. and U.K. populations.
A decline has been additionally noted in the utilization of antiosteoporotic drugs for primary osteoporosis prevention. One explanation for this trend appears to be recent changes in U.S. reimbursement and massive inflation, as well as concern about possible rare, long-term side effects of bisphosphonate treatment, such as the occurrence of osteonecrosis of the jaw and atypical femoral head fractures.
The role of the family doctor29-32
As time goes on, the elderly man accumulates more and more diseases. It is estimated that after 60 years, the elderly have an average of 4-5 chronic diseases, but their number may be even higher because some diseases facilitate the appearance of others.29
However, some of these diseases will be more common in the elderly due to decreasing the body's means of defense and repair. These diseases include osteoporosis.
The family doctor must make a diagnostic and therapeutic synthesis, i.e., to diagnose all diseases and make a hierarchy of them because some are more serious than others, and there is the possibility of not treating them simultaneously.
The aging process affects the whole body, and the elderly have several associated diseases, and the family doctor must perform a full consultation of the patient to insist on certain aspects specific to the elderly.31
In this regard, the doctor must make a meticulous observation of the patient regarding the position, attitude, nutritional status, facial expression, gait, balance, ease or weight with which he gets up from the chair, the state of hygiene, how he is dressed and others. During the anamnesis, the family doctor will have to assess the patient's voice, mode of expression, neuropsychic condition, orientation in time and space, memory, thinking, current allegations, pathological history, treatments followed, the natural history of the diseases they present, conditions of life, the autonomy capacity of the elderly man, the socio-economic situation and others.
At the entire physical examination of the patient, the family doctor will have to insist on age-specific diseases, geriatric syndromes, the complications that chronic diseases could produce, and the side effects that treatments could produce, which they follow.
Often the cooperation of the family is necessary, with which the family doctor must be able to communicate, because the compliance of the elderly can be influenced by several factors, such as memory disorders, confusion, hearing impairments, visual impairments, tremors, lack of understanding, delusions, comorbidities.29
Family physicians adhered more to different areas of osteoporosis management than in 2007 (baseline survey). Knowledge of risk factors for osteoporosis has been improved in part due to educational activities. targeting GPs and to the updated and adapted guidelines.29
Self-estimated relative adherence to secondary prevention was reported. Family physicians outlined that they are seriously involved in post-fracture care, i.e., recommendations such as referral to a specialist, lifestyle changes, prescribing calcium/vitamin D supplements, prevention of falls.
However, family history and awareness of calcium, zinc and vitamin D intake21 were still insufficient. Systemic regulations, such as issuing prescribing conditions, less stringent annual budget limits based on prescriptions, and the influx of generic bisphosphonates, have likely helped a great deal in removing significant obstacles to managing osteoporosis perceived by family physicians.29
Osteoporosis and bone fragility are widespread conditions of great importance in the worldwide health system care. Family doctors contribute to global strategy programme for the prevention and medical treatment of osteoporosis and its consequences.
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27. Tsuda E, Fukuda C, Okada A, et al. Characterization, pharmacokinetics, and pharmacodynamics of anti-Siglec-15 antibody and its potency for treating osteoporosis and as follow-up treatment after parathyroid hormone use. Bone. 2021:116241.
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28. Shin YH, Shin WC, Kim JW. Effect of osteoporosis medication on fracture healing: an evidence based review. J Bone Metab. 2020;27:15-26.
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29. Vytrisalova M, Touskova T, Fuksa L, et al. How general practitioners and their patients adhere to osteoporosis management: a follow-up survey among Czech general practitioners. Front Pharmacol. 2017;8:258.
https://doi.org/10.3389/fphar.2017.00258
30. Poivret D, Goetz C, Zevering Y, Wilcke C, Noirez V. Effect of patient-led cooperative follow-up by general practitioners and community pharmacists on osteoporosis treatment persistence. Int J Rheum Dis. 2021;24:912-21.
https://doi.org/10.1111/1756-185X.14146
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