Keywords
hypophosphatemia - rickets - X-linked hypophosphatemia (XLH) - genetic bone diseases
- metabolic bone diseases - rare bone diseases - Burosumab
Introduction
Rare endocrine-metabolic diseases represent an important area in medicine and pharmacology.
The rare diseases of particular interest to endocrinologists involve all fields of
endocrinology with the possible involvement of multiple endocrine glands.[1] Bone and mineral diseases encompass various conditions that involve altered skeletal
homeostasis and are frequently associated with changes in circulating calcium, phosphate,
or vitamin D metabolites.[2] They are commonly associated with severe clinical consequences and have a genetic
etiology.[3]
[4] Diagnosing these disorders requires a detailed clinical assessment of the wide variety
of symptoms and signs associated with these diseases. Thus, clinicians should be aware
of the relevant features of a careful history and physical examination, followed by
appropriate laboratory and skeletal imaging investigations.[5] Finally, clinicians should be familiar with the range of molecular genetic tests
available to ensure appropriate use and interpretation.[4]
[5]
Although genetic and metabolic bone diseases present more often during early childhood,[1]
[2]
[3] they may also be seen in similar or different forms in adolescence and adulthood.[6]
[7] The rare nature of these conditions may lead to late recognition, low diagnostic
rates, and inadequate or inappropriate management. Recent advances enabled more diagnostic
and management opportunities for many of these conditions. For example, X-linked hypophosphatemia
(XLH) is the commonest form of inherited hypophosphatemia, caused by a mutation in
the PHEX gene, leading to excessive expression of the phosphaturic factor FGF23. Symptoms
are chiefly related to rickets in children and osteomalacia in adults causing several
complications that can be highly invalidating.[8] Perhaps due to its rarity, XLH is poorly known, and diagnosis may frequently be
delayed despite the availability of comprehensive national, regional, and international
guidelines.[9]
[10]
[11] Conventional treatment has been based on oral phosphate salt supplementation and
activated vitamin D analogs which cannot cure the disease. Over the past decade, several
advanced treatment options have been introduced and shown to be effective for many
metabolic bone disorders, such as Burosumab for XLH.[12] On the other hand, other disorders remain under-recognized in many world regions.
Therefore, familiarity with these rare endocrine diseases remains a crucial factor
in the early recognition and diagnosis of physicians who are likely to contact such
patients during childhood, adolescence, and adulthood.
Surveying physicians' perceptions, attitudes, and practices is a commonly used approach
or proxy method for assessing disease burden and care provision and exploring the
role of innovative work behavior in health care with particular relevance to rare
disorders.[13]
[14]
[15] Several surveys on the management pattern of common endocrine conditions in the
Middle East and Africa (MEA) region have been recently conducted.[16]
[17]
[18] In the present study, we wished to scope the awareness and perception of physicians
in the MEA region concerning certain genetic and metabolic bone diseases in general
and XLH as an example of a condition with both conventional and specific therapy.
The principal aim was to provide baseline information/data to direct future education.
Materials and Methods
This survey aimed to assess the level of awareness of physicians from two developing
regions concerning certain genetic and metabolic bone diseases in general and XLH
in particular. The survey included diagnosis, conventional management, and recent
advances. A cross-sectional electronic survey was conducted between July and December
2019.
A focused literature search on the study area was undertaken to work with a writing
group for a related article.[11] Another survey conducted in Europe with similar objectives was also reviewed. A
questionnaire based on the search inspired by the above survey was adopted and finalized
after attending an in-depth workshop on XLH at a rare disease center in Paris.[19] The questionnaire was converted into an online version by a commercial software
provider. Some additional questions are deemed necessary for the target regions of
interest. Due to the dual objectives of the survey, the questions were organized from
general to more focused and specific areas to avoid giving hints. The questionnaire
consisted of multiple-choice questions, including free-text answers for some open
questions. The [Supplementary Material] ([Supplementary Appendix 1] [available in the online version]) provides the survey questions and predetermined
responses. After obtaining informed consent, the survey then presented the participants
with 20 questions arranged in 5 domains: (I) demographic and professional profile
(8); (II) awareness of rare genetic/metabolic bone disease (2); (III) awareness of
XLH (2); (IV) Symptoms of XLH (3); and (V) management of XLH (5).
A web-based commercial survey management service (Survey Monkey, Palo Alto, California,
United States) was used. All participants received an initial email that explained
the rationale of the survey and what was required from the consented respondents,
followed by three subsequent reminder emails during the study period. Each message
included an explanation of the rationale and method of participation, full credentials,
and contact details of the principal investigator, together with a unique email-specific
electronic link to the questionnaire. The survey service automatically blocked repeated
submissions from the same IP address. The voluntary nature of the contribution, the
unconditional right to decline participation and opt-out from the database, and the
confidentiality of participant details were all confirmed. Data were collected anonymously,
and the questionnaire text was available in English and French, the two languages
used by medical professionals in the target regions. The survey Web site was open
for the 6-month study period from July 1, 2019 to December 31, 2019. In the end, survey
responses were collected and stored electronically for an anonymous analysis.
In the absence of a single MEA regional endocrine society with a membership list that
can define a study population, the target population was identified from a list of
electronic mails pooled from continuous professional development delegates, speakers,
authors, or members of various scientific groups or forums in various parts of the
MEA region. Consequently, several questions were added to the survey to help define
the demographic and professional profiles of the respondents and their practices,
similar to our previously published studies.[16]
[17]
[18]
Summary statistics were prepared for responses to each question. Because not every
participant answered all questions, the percentage of respondents providing a given
answer was calculated individually for each question, using the number of respondents
to that question in the denominator.
Results
Respondents' Demographic and Professional Profiles
A total of 262 responses were received, of which 139 were deemed analyzable. Nonrespondents,
those who declined consent, and those with substantially inadequate answers were excluded
from the analysis. The largest proportion, 58 (41.7%), practiced in the Arabian Gulf,
28 (20.1%) in the rest of the Middle East, 24 (17.3%) in North Africa, and 29 (20.9%)
respondents were from Sub-Saharan Africa. The demographic and professional profiles
of the participants are detailed in [Table 1]. The largest specialty represented was endocrinology, with 41% of respondents (adult
35.3%, pediatric 5.7%), followed by 23 general physicians or pediatricians with an
interest in endocrinology (16.5%) and 14 (10.1%) primary care physicians ([Table 1]). Of the group as a whole, 53 (38.1%) treat adults only, 55 (39.6%) treat children
only, and 31 (22.3%) manage both age groups. Among the respondents, 33 (23.7%) have
been in clinical practice for 10 years, whereas 27.3 and 28.1% have been in clinical
practice for 11 to 20 and 21 to 30 years, respectively. The majority of respondents
(71.2%) were senior physicians. Over two-thirds of respondents (68.5%) practice in
tertiary level centers, and 15.8% practice in district or community hospitals/polyclinics.
The proportion of time spent in direct patient care, as opposed to research, teaching,
and administration, was 75 to 53.2% ([Table 1]).
Table 1
Demographics and professional profiles of the respondents
|
Questions and potential responses
|
Results
|
|
Please indicate the age group you manage:
|
|
Adults only
|
53 (38.1%)
|
|
Children only
|
55 (39.6%)
|
|
Both
|
31 (22.3%)
|
|
How best you describe your specialty:
|
|
Endocrinologists (adult and pediatric)
|
57 (41.1%)
|
|
Medicine/pediatrics with endocrine interest
|
23 (16.5%)
|
|
Primary care physicians
|
14 (10.1%)
|
|
All other specialties not listed
|
13 (9.4%)
|
|
General pediatrics
|
11 (7.9%)
|
|
General internist
|
10 (7.2%)
|
|
Nephrologists (adult or pediatric)
|
4 (2.9%)
|
|
Rheumatologists and orthopaedic surgeons
|
4 (2.8%)
|
|
Neurologists (adult or pediatric)
|
3 (2.2%)
|
|
Number of years have been in practice since graduation:
|
|
<10 years
|
22 (23.7%)
|
|
11–20 years
|
38 (27.3%)
|
|
21–30 years
|
39 (28.1%)
|
|
31–40 years
|
20 (14.4%)
|
|
>40 years
|
9 (6.5%)
|
|
Current professional career stage:
|
|
Senior (consultant/attending)
|
99 (71.2%)
|
|
Mid-grade (specialist/fellow)
|
40 (28.8%)
|
|
Nature of clinical practice setting:
|
|
University or teaching hospital/specialized center (tertiary)
|
95 (68.3%)
|
|
District or community (nonteaching) hospital/polyclinic
|
22 (15.8%)
|
|
Primary care/family medicine
|
16 (11.5%)
|
|
Other services (police, army, employer-based)
|
6 (4.3%)
|
Awareness of Rare Genetic/Metabolic Bone Disease and XLH
The detailed responses to the two questions included in this section are shown in
[Table 2]. When asked, “thinking of metabolic/genetic bone diseases, which specific diseases,
if any, come to mind? 16 (11.5%) responded that they do not know about any metabolic/genetic
bone diseases, and 123 respondents (88.5%) stated that they could think of some metabolic/genetic
bone diseases and of these 111 respondents enumerated various genetic and metabolic
disorders. The top five responses in decreasing frequency were: osteogenesis imperfecta
(44), osteoporosis (31), rickets (23), osteomalacia (22), and achondroplasia (11).
Table 2
Awareness of rare genetic/metabolic bone disease and XLH in physicians whose patients
are adults and those whose patients are mostly in the pediatric age group
|
Questions and potential responses
|
Responses by age group of treated patients
|
|
Adults
|
Pediatric
|
|
When thinking of metabolic/genetic bone diseases, which specific diseases, if any,
come to your mind:
|
|
I do not know of any:
|
7 (13.2%)
|
4 (7.3%)
|
|
I can think of some:
|
46 (86.8%)
|
51 (92.7%)
|
|
Please take a moment to read the disease description and list of symptoms detailed
in [Fig. 1]. What disease do you think this description refers to?
|
|
I do not know:
|
14 (26.4%)
|
4 (7.3%)
|
|
I have some idea about the condition
|
39 (73.6%)
|
9 (2.7%)
|
|
Have you heard of a metabolic bone disease called XLH?
|
|
Yes
|
41 (83.7%)
|
55 (100%)
|
|
No
|
8 (16.3%)
|
0 (0%)
|
|
How did you hear about it for the first time?
|
|
From own readings.
|
26 (53.1%)
|
14 (25.5%)
|
|
I looked after a patient or suspected patient.
|
9 (18.4%)
|
9 (16.4%)
|
|
It was mentioned in a discussion about a patient.
|
7 (14.3%)
|
27 (49.1%)
|
|
It was mentioned in a lecture/presentation.
|
1 (2.0%)
|
1 (1.8%)
|
|
I have attended a meeting on XLH or rare bone disorders.
|
1 (2.0%)
|
3 (5.5%)
|
|
I received an email alert about it.
|
2 (4.1%)
|
0 (0%)
|
|
It was mentioned to me by a medical representative.
|
3 (6.1%)
|
1 (1.8%)
|
|
If there were a biological treatment available specifically for XLH, would you be
more likely to refer patients for treatment?
|
|
Yes
|
40 (85.1%)
|
51 (94.4%)
|
|
No
|
7 (14.9%)
|
3 (5.6%)
|
Abbreviation: XLH, X-linked hypophosphatemia.
Awareness of Respondents of the Symptoms and Management of XLH
In the second question, respondents were given a typical case scenario suggestive
of XLH ([Fig. 1]). The responses are detailed in [Table 3]. Twenty-five respondents (18.0%) indicated not knowing what disease this description
refers to, whereas 114 (82.0%) stated they had some idea about the condition. Of the
latter group, 109 provided suggestions for a possible diagnosis. When respondents
were asked if they had heard of a metabolic bone disease called XLH, 120 of 135 (88.9%)
confirmed that they had heard about it before, and 15 (11.1%) had not heard of XLH
before. Of those who confirmed some prior knowledge of XLH, 45.0% were aware of it
through independent reading, and 30.8% had come across the disease in the context
of patient care or managing a patient suspected of having a bone mineral disease or
XLH; 15.8% stated that they had seen it mentioned in a lecture/presentation, 3.3%
stated they had attended a special meeting on XLH or rare bone disorders (3.3%), and
the remaining respondents stated they had heard of it from a colleague in a discussion
about a patient or mentioned by a medical representative. Pediatric physicians tended
to have a more in-depth awareness of practical-based knowledge than adult physicians.
To evaluate the perceived frequency of encountered symptoms compatible with XLH and
how they manage them, three questions were asked. First, the respondents were asked
if they had seen patients without a firm diagnosis and a few symptoms, listed below,
in the previous 12 months. The responses included short stature (by 65.9%), lower
limb deformity (by 56.6%), bone or joint pain (by 53.5%), weakness/fatigue (51.2%),
fractures (41.9%), active dental problems (33.3%), and previous corrective osteotomies
or joint replacements (21.7%). Next, the respondents were asked how many patients
without a firm diagnosis could be consistent with the following symptoms (short stature,
lower limb deformity, bone or joint pain, weakness/fatigue, fractures, active dental
problems, previous corrective osteotomies, or joint replacements) have they seen in
the last 12 months? The responses (129) were no patients (31.8%), 1 to 3 patients
(48.8%), 4 to 6 patients (9.3%), 7 to 12 patients (3.9%), and more than 12 patients
(6.5%). Furthermore, respondents were asked how many patients that you selected in
the previous question (i.e., without a firm diagnosis that you have seen in the previous
12 months, based on the following symptoms: short stature, lower limb deformity, bone
or joint pain, weakness/fatigue, fractures, active dental problems, previous corrective
osteotomies, or joint replacements) could have XLH? Nearly half of the respondents,
61/129 (47.3%), thought none. Other responses included one patient (22.5%), two patients
(14.7%), three patients (5.4%), four patients (2.3%), more than five (4.7%), and others
(3.1%).
Fig. 1 The index case of typical case scenario suggestive of XLH provided to form the basis
of the survey section on XLH.
Table 3
Awareness of respondents of the symptoms and management of XLH
|
Questions and potential responses
|
Responses by age group of treated patients
|
|
Adults
|
Pediatric
|
|
Have you seen patients without a firm diagnosis who would be presented with a couple
or a few of the symptoms below in the last 12 months? (Check all that apply):
|
|
Short stature
|
23 (48.9%)
|
46 (83.6%)
|
|
Lower limb deformity
|
19 (40.4%)
|
41 (74.5%)
|
|
Bone or joint pain
|
31 (66.0%)
|
25 (45.5%)
|
|
Weakness/fatigue
|
27 (57.4%)
|
24 (43.6%)
|
|
Fractures
|
19 (40.4%)
|
22 (40.0%)
|
|
Active dental problems
|
9 (19.1%)
|
25 (45.5%)
|
|
Previous corrective osteotomies or joint replacements
|
8 (17.0%)
|
16 (29.1%)
|
|
How many patients without a firm diagnosis, who would be consistent with the symptoms
listed above have you seen in the last 12 months?
|
|
None
|
21 (44.7%)
|
9 (16.4%)
|
|
1–6
|
13 (48.9%)
|
38 (68.1%)
|
|
>6
|
3 (6.4%)
|
8 (14.6%)
|
|
Are there any patients in your care who are currently being investigated or screened
for XLH?
|
|
Yes
|
5 (10.6%)
|
29 (53.7%)
|
|
No
|
42 (89.4%)
|
25 (46.3%)
|
|
From practical experience or general knowledge, which of the following did you (or
would you) use to treat XLH?
|
|
Phosphate supplements
|
31 (66.0%)
|
43 (79.6%)
|
|
Vitamin D preparations (either alfacalcidol or calcitriol)
|
31 (66.0%)
|
47 (87.0%)
|
|
Pain medications: (opiates or nonopiates)
|
13 (27.7%)
|
17 (31.5%)
|
|
Biologics
|
3 (6.4%)
|
1 (1.9%)
|
|
Burosumab
|
9 (19.1%)
|
17 (31.5%)
|
|
No treatment is usually needed
|
1 (2.1%)
|
0 (0%)
|
|
No treatment available
|
0 (0%)
|
0 (0%)
|
|
Other
|
0 (0%)
|
2 (3.7%)
|
|
If there were a biological treatment available specifically for XLH, would you be
more likely to refer patients for treatment?
|
|
Yes
|
40 (85.1%)
|
51 (94.4%)
|
|
No
|
7 (14.9%)
|
3 (5.6%)
|
Abbreviation: XLH, X-linked hypophosphatemia.
First, respondents were asked if they had any patients being investigated or screened
for XLH at the time of the survey. Most of the respondents (90/128, 70.3%) had no
patients, and only 38 respondents (29.7%) confirmed having patients in this category.
Second, from their practical experience or general knowledge, they were asked to name
which treatments to use in patients with a potential diagnosis of XLH. In a decreasing
order of frequency, the top three responses included: active vitamin D analogs such
as alfacalcidol or calcitriol (75.8%), phosphate supplements (71.1%), and pain control
medications including opiates or nonopiates (32.0%). Burosumab was identified by 25.8%
of respondents. Other therapies were chosen by a minority, including biologics (5.5%);
the remaining respondents stated that neither treatment is available, needed (3.2%),
nor provided (4.7%). When respondents were also asked if they would be more likely
to refer patients for treatment if a biologic therapy was available specifically for
XLH, 89.8% confirmed they would refer patients to others. There was a trend for pediatric
physicians to undertake more roles in management and treatments, whereas adult physicians
tended to undertake diagnosis and referrals ([Table 4]).
Table 4
Respondents' views on the organization of care for patients suspected or confirmed
to have XLH
|
Questions and potential responses
|
Responses by age group of treated patients
|
|
Adults
|
Pediatric
|
|
What would be your primary role in managing patients who have symptoms consistent
with XLH?
|
|
Diagnosis
|
26 (55.3%)
|
38 (70.4%)
|
|
Treatment
|
15 (31.9%)
|
27 (50.0%)
|
|
Management
|
19 (40.4%)
|
38 (70.4%)
|
|
Referral
|
26 (55.3%)
|
20 (37.0%)
|
|
Other
|
1 (2.1%)
|
0 (0%)
|
|
To whom would you refer XLH patients for treatment with the biologic described in
the above question?
|
|
Family medicine physician
|
2 (4.3%)
|
2 (3.8%)
|
|
Pain specialist
|
3 (6.4%)
|
5 (9.4%)
|
|
Endocrinologist
|
37 (78.7%)
|
38 (71.7%)
|
|
Nephrologist
|
4 (8.5%)
|
17 (32.1%)
|
|
Rheumatologist
|
19 (40.4%)
|
5 (9.4%)
|
|
Orthopaedic surgeon
|
7 (14.9%)
|
16 (30.2%)
|
|
Other
|
3 (6.4%)
|
2 (3.8%)
|
Abbreviation: XLH, X-linked hypophosphatemia.
Perceived Professional Roles in Delivery and Organization of Care
The perceived roles in the delivery and organization of care of patients with symptoms
consistent with XLH are shown separately for adult and pediatric physicians in [Table 4]. Out of 128 respondents, 62.5% considered their role mainly in diagnosis, 53.1%
stated they felt their primary role was in general management, 46.9% in making a referral,
and 40.6% would be involved in actual treatment (40.6%). Furthermore, respondents
indicated that they would refer to the following four specialties (either pediatric
or adult) of any XLH patient for treatment with biologic therapy if available: in
a decreasing frequency, endocrinology, rheumatology, orthopaedic surgery, and nephrology,
but less likely to refer to a pain clinic or other specialties. Physicians dealing
with the pediatric age group favor more referrals to nephrologists and orthopaedic
surgeons ([Table 4]).
Discussion
The current report provides a survey of physicians practicing in the MEA region regarding
their general awareness of the burden and clinical management of genetic and metabolic
bone disorders and their awareness, knowledge, and management of XLH. In particular,
we have used an analogous survey instrument previously employed in an international
survey tested as a market research tool in Europe (personal communication).
Most respondents were qualified endocrinologists or physicians interested in endocrinology
in many countries, providing a comprehensive view of the region, albeit not homogeneously.
Our respondents treat both adult and pediatric age groups. At least one-third had
been in practice for 10 years, and over one-half have been practicing between 11 and
30 years. Therefore, our participants are likely to represent physicians who may look
after suspected and confirmed cases of XLH.
Due to the low prevalence of XLH, awareness and knowledge of the physicians are paramount
to drive screening, identification, and referral to management and may need innovative
work behavior.[14] For instance, the experts' opinion survey conducted across Italian centers collected
data on XLH epidemiology, diagnosis, and treatment using a questionnaire reflecting
175 patients' data over 20 years.[15] The diagnosis was made chiefly during childhood. The authors underscored that XLH
remains a severe condition with significant morbidity, multiple presentations, and
variable treatment approaches.[15] The situation may be particularly relevant in the MEA region, where the medical
profession may not be structured similarly to developed countries.
A recent study included pediatric endocrinologists exclusively and may not reflect
the broader image.[20] In the present study, although 88.9% of participants had heard about XLH, their
awareness of the symptoms was limited. This may result in a lack of credibility as
patients may hesitate to take further advice from nonexpert health care professionals
with no in-depth knowledge about XLH. A recent detailed interprofessional mixed-methods
study on adults living with XLH revealed that they are experiencing, among other concerns,
chronic pain and fear of falling.[21] There are no data of this nature from the MEA region. We would, however, expect
similar problems from the local patient population, particularly if faced with health
care providers with no experience in XLH management. Therefore, it is imperative to
raise health care providers' awareness about the impact of such conditions on patients'
well-being. To this end, the present study and that of Deeb et al are valuable needs-assessment
exercises for identifying gaps in the knowledge to help in planning education and
training activities.[20] The two studies targeted slightly different populations with some overlap and used
instruments with different emphases. Thus, their results should be viewed as complementary.
Only a third of the responders had encountered a patient living with XLH or suspected
of the disease. This may be attributed to the low rates of identification and confirmation
of the diagnosis, particularly a noticeable number of the respondents who practice
in tertiary hospitals and are in the most relevant specialty, endocrinology. Alternatively,
it may be an utter reflection of the condition's rarity in general. Notwithstanding,
the higher rates of consanguinity furniture for increased rates of inherited genetic
conditions have been well documented in many parts of the region. For instance, data
from Qatar suggest a significant role of parental consanguinity in increasing the
prevalence of genetic disorders, mainly autosomal recessive disorders.[22] Also, this issue was elaborated further with many lessons learned from a large-scale,
first-tier clinical exome sequencing in a highly consanguineous population in Saudi
Arabia.[23] These observations argue for the practice and research relevance of the present
study. Although the prevalence of disease in MEA is not known precisely, there is
a fair volume of information in several case reports and presentations in conferences
and workshops.[24]
[25]
[26]
[27]
[28]
[29]
Only a quarter of the respondents were aware of Burosumab, approved by the American
and European regulatory bodies in 2018.[30] Burosumab is now a standard approach in all guidelines and expert opinions.[9]
[10]
[11]
[12] A minority of respondents in the present study had patients with XLH in their clinics.
Nonetheless, it is reassuring that most of them included suspected hypophosphatemic
rickets as the likely diagnosis in the survey's case scenario, although many considered
osteogenesis imperfecta at the top of their differential diagnosis. Many of them are
aware of XLH, and around 70 to 75% were aware of the mainstay of conventional therapy.
Although this was an indirect question, most respondents perceive conventional therapy
as inadequate for XLH as 89.8% confirmed that they would refer for more specific treatment
if it existed. This concurs with the findings of Deeb et al, who posed this question
more directly.[20] Previous studies of physicians and patients addressed the reasons behind the perceived
inadequacy of conventional treatment.[15]
[21] These included poor compliance related to multiple doses, gastrointestinal side
effects and unfavored palatability, reduced final height persistence of skeletal deformities,
and appearance of nephrocalcinosis as a complication. In the other regional survey,
the most familiar suggested reasons for the inadequacy of conventional treatment were
reduced final height, inability to revert skeletal deformities, poor compliance, and
associated nephrocalcinosis.[20] We have not included such details in more depth in our survey, as our target population
was much more comprehensive, and it was felt inappropriate.
The present study has some limitations worthy of note. First, it is limited by its
nature of a survey of reported perceptions and recalled patterns of practice rather
than an actual quality assurance using preset key performance indicators. Second,
the number of responders is relatively tiny. Third, the sample is not homogeneously
representative of the targeted region. Nonetheless, the survey provides a baseline
bird's eye view of the level of awareness and recognition, including mixed participants
from pediatric and adult physicians, of XLH in the MEA region. It underscores some
gaps in the knowledge of this genetic condition. The information can be used to develop
focused, continuous professional development programs for physicians likely to be
involved in XLH care.
Conclusion
Physicians in the MEA region are reasonably aware of XLH but have variable perceptions
and expected practices. They are largely unsatisfied with its conventional treatment,
and the majority are prepared to refer patients for more specific treatment if available.
Endocrinologists view the care of XLH as appropriate for their specialty and seem
keen to keep its management within the endocrine practice. Raising awareness of the
recognition and modern management of XLH is needed. The formation of rare bone diseases
or XLH interest groups within existing regional bodies, unconditionally supported
by the pharmaceutical and scientific industry, would define the epidemiology, enhance
knowledge, and maintain a seamless contact with international forums and centers of
excellence that should translate to better patient care in the region.
