Advice and guidance for primary care

Most patients with Fibromyalgia/Widespread Pain can be safely diagnosed and treated in primary care.

Consider diagnosis of Fibromyalgia if the patient has:

• Widespread pain generally symmetrical NOT restricted to specific joints or muscle areas
• Unrefreshed sleep
• Excess fatigue
• Poor memory and concentration
• Examination – no joint swelling, hypermobility or (significant) restriction
• Symmetrical tenderness to pressure or movement of most joint and muscle regions
• Hyperalgesia: excessive sensation or pain response to a minor mechanical stimulus
• Normal bloods (see below for screen)
• May have had numerous attendances for different symptoms with nil on previous investigations

Not if:

• Evidence of active synovitis
• Raynauds, Sicca symptoms
• Troublesome mouth ulcers
• Rash or sun sensitivity, Hair thinning

Only consider referral to Integrated MSK, Pain & Rheumatology (IMPReS) single point of access (SPOA) for more complex presentations from a diagnostic point of view or if patient is struggling to manage their symptoms (Pain Mangement). Referrals received without the above may be returned.

Expectations of the GP - diagnosis and management

Firstly:

• To complete baseline bloods
• FBC ESR CRP TSH Creatinine Kinase, Calcium, Alk Phos, U&E
• Vitamin D in high risk patients

Secondly:

• To explain diagnosis and self-management strategies/support without referring on for a Specialist opinion
• Direct patient to relevant self-help information (self-help links below)

Please note pain symptoms in the absence of specific features suggestive of inflammatory arthritis or autoimmune disease should not prompt a referral to rheumatology

Self-help links

Versus Arthritis - Fibromyalgia

Patient UK - Fibromyalgia

Pain Tool Kit by Pete Moore

Assessment and referral of the patient with suspected hypermobility/hypermobility spectrum disorder

This information can be downloaded as a Word file.

A note for referrers

• The IMPReS (including MSK, Pain and Rheumatology departments) do not offer a diagnostic service for Ehler-danlos Syndrome or hypermobility spectrum disorders (HSD).
• Symptomatic patients with hypermobility spectrum disorder (HSD) or hypermobile Ehlers Danlos syndrome (hEDS) can generally be diagnosed and often managed in primary care. They are not at risk of serious medical complications from their condition. These patients do not require a referral to a rheumatologist as HDCTs are neither inflammatory nor autoimmune conditions.  They do not require referral to a geneticist as there is no genetic test for HSD or hEDS.
• If Classical EDS (cEDS) or Vascular EDS (vEDS) is suspected, please refer to directly to genetics or to dermatology/cardiology if there is diagnostic uncertainty after initial primary care workup.
• Rare and serious subtypes of EDS may require referral to a geneticist and often a non-rheumatology specialist to investigate and manage the non-joint related complications from their condition.

Suggested Primary care workup

• Assess for joint hypermobility using a validated scoring system for example the Beighton’s score

• Examine the skin for scarring, haemosiderin deposits, abnormal elasticity, abnormal translucency

• Examine the cardiovascular system. Specifically ask about a family history of early cardiovascular related death
• Assess the patient for features of Marfans syndrome against the Ghent criteria

Referral pathways

• In symptomatic generalised hypermobility please refer to physiotherapy for advice and self-management (if the patient is happy to engage)
• For patients presenting with fibromyalgia type general widespread pain along with hypermobility, please direct to appropriate resources for FM e.g. Versus Arthritis
• When referring to the physiotherapy department, you will be asked to confirm a Ghent score < 7, no concerning skin features suggestive of cEDS or vEDS, and no concerning cardiovascular findings on clinical examination
• If the patient is struggling to manage their symptoms despite physiotherapy and self-management, please consider a referral to pain clinic
• If the Ghent score is over 7 refer to genetics for suspected Marfans syndrome
• If the dermatology assessment is consistent with cEDS or vEDS refer to genetics or refer to dermatology if the diagnosis is in doubt
• If the cardiovascular assessment is abnormal refer to cardiology or if vEDS is suspected, refer to genetics

Hypermobility spectrum disorders (HSD) and hereditary disorders of connective tissue (HDCT)

Hereditary disorders of connective tissue (HDCT) are caused by abnormalities in the structure or synthesis of extracellular matrix molecules for example collagen, elastin and muco-polysaccharides.

Symptomatic patients with hypermobility spectrum disorder (HSD) or hypermobile Ehlers Danlos syndrome (hEDS) are not at risk of serious medical complications from their condition. They can therefore generally be diagnosed and often managed in primary care.

These patients do not require a referral to a rheumatologist as HDCTs are not inflammatory or autoimmune conditions (Islam et al 2020). Neither do they require referral to a geneticist as there is no genetic test for HSD or hEDS.

There is no cure for hypermobility but support and advice may be helpful. Support may be via written or audio information, physiotherapy or pain management services.

Rare and serious subtypes of EDS may require referral to a geneticist and often a non-rheumatology specialist to investigate and manage the non-joint related complications from their condition (Islam et al 2021)

Please note HDCTs are distinct from connective tissue diseases (CTDs) such as SLE, Sjogrens or systemic sclerosis. CTDs are autoimmune and inflammatory disorders which should be referred to rheumatology

Diagnosing hypermobility

There are several scoring systems in use all with advantages and disadvantages

Although not originally intended for clinical use, the Beighton score is the most commonly used as it is quick to perform and has been validated for generalised hypermobility. It is important that the relevant joints are assessed correctly so as not to overestimate the score.

The following video on the Beighton score is helpful.

https://www.physio-pedia.com/Beighton_score

Generalised hypermobility is typically diagnosed if the score is 4 or more out of 9 in adults. However

if limits are defined such that 95% of normal people in a population lie within a normal range i.e. are normally mobile, it has been suggested that adult females of European ancestry below 40 years should have a Beighton score of 5 or greater to be defined as hypermobile. This is the score used at ELHT in this cohort.

If using the Beighton’s score, the clinician should also examine those joints which the patient flags as problematic if not included in the score. For example the shoulder is one of the commonest joints to sublux and dislocate and many patients report hand joint problems. If necessary an alternative scoring system for example the Hospital Del Mar criteria which assesses a greater number of joints (Domingos 2019)

If the patient does not fulfil criteria for generalized hypermobility then consider alternative causes for their symptoms.

Identifying those patients who may need to see a geneticist or a secondary care specialist.

Marfans syndrome

Marfans syndrome is associated with a mutation of the fibrillin 1 gene on chromosome 15. Patients with MFS may present with hypermobility often in association with morphological abnormalities.

Any patient with a Revised Ghent Nosology score over 7 should be referred to genetics for testing

https://orthotoolkit.com/systemic-score/

https://marfan.org/dx/score/

Vascular EDS

Vascular EDS is a rare but serious form of EDS. Complications of the condition include

• organ rupture, for example the large bowel or pregnant uterus
• Fragile blood vessels leading to dissections and ruptures

Other features include:

• Thin translucent skin such that small blood vessels are highly visible especially on the upper chest and legs.Hypermobility, predominantly in small joints
• Premature aging of the skin on hands and feet
• Abnormal facies, including a thin nose and lips, large eyes, small earlobes and fine sparse hair
• talipes
• Pneumothorax
• Early onset severe varicose veins

https://www.ehlers-danlos.org/information/vascular-ehlers-danlos-syndrome/

If a patient has a history of otherwise unexplained organ rupture or significant vessel fragility, it is likely that the patient will be referred directly to genetics from the relevant speciality.  For assessment of skin changes which may be indicative of vascular EDS, seek the opinion of a dermatologist.

Classic type EDS

Skin changes are very helpful in diagnosing EDS. In fact Edvard Ehlers was a Danish dermatologist and Henri-Alexandre Danlos was a French physician with an interest in skin disorders (Stembridge et al 2022).

In Classic type EDS there is abnormal elasticity and extreme fragility of the skin.

Skin hyperextensibility can be assessed over the elbows and knees, and extensibility of 3 cm or more at these sites is suggestive of cEDS (Stambridge 2022). At the volar forearm with an extended wrist, the skin may stretch over 1.5cm in cEDS. The neck is less reliable in older individuals due to age related non-elastic stretching of the skin.

Other skin changes of cEDS include

• atrophic scarring -the scar is sunken, and often wider than the original wound,
• significant skin lacerations from minor trauma
• easy bruising
• hemosiderin deposits in old scars.

https://www.youtube.com/watch?v=5ZJzXrgN0gE Dr Nigel Burrows

Milder skin changes may be seen in HSD and hEDS for example soft, mildly hyperextensible skin, unexplained striae and mild atrophic scarring. Significant papyraceous scars and haemosiderin deposits is not seen.

If the diagnosis is in doubt then refer to dermatology.

Cardiovascular assessment

A cardiovascular history and examination is appropriate in patients with hypermobility. A family history is important including details of sudden deaths.

Patients with Marfans syndrome, angiodysplasia and vascular EDS may have abnormal examination findings.

For patients with general HSD or hEDS several studies have suggested there is no increased risk of cardiac abnormalities. An echo is not therefore required in the presence of a normal cardiovascular clinical examination (Paige et al 2020).

It has been suggested there may be an association between hypermobility and postural orthostatic tachycardia syndrome. A definite link has not to date been established however. For symptomatic patients suspected of having POTS, a screening assessment can be carried out  in primary care and a referral arranged to cardiology if positive. It is important to ensure that the tachycardia does not occur at the time of instruction to stand rather than actual standing – the former may indicate an acquired stress response to a prior vaso-vagal episode (Norcliffe-Kaufmann et at 2022).

https://www.potsuk.org/about-pots/diagnosis

Mast Cell activation syndrome (MCAS)

Studes have shown there may be a link between HSD, POTS and MCAS. However an evidence based common pathological or physiological association between these conditions has not yet been established with certainty (Kohn and Chang 2020).

Should there be concern about possible MCAS symptoms, the advice of an immunologist, not a rhematologist should be sought.

HSD/ h(EDS)/ Fibromyalgia (FM)

The diagnostic criteria for hEDS are detailed here

https://www.ehlers-danlos.com/what-is-eds/hypermobile-ehlers-danlos-syndrome-heds/#1677083905021-223e2d3a-6c22

If a medically confirmed positive family history is known, many patients with generalised hypermobility, chronic widespread pain and mild skin changes will fulfil the above hEDS criteria.

Despite widespread symptoms patients may experience, they can still be reassured that serious cardiovascular sequelae are not associated with HSD or hEDS.

It is widely recognised that many patients presenting with hypermobility, have symptoms which are similar to those presenting with a primary pain disorder e.g. fibromyalgia

It is not clear in an individual patient whether they have coincidental fibromyalgia (FM) and generalised hypermobility (both conditions are relatively common so would be expected to co-exist in some) or if the hypermobility is a trigger for widespread pain, particularly as the causes of fibromyalgia itself are not known, but increasingly this looks like a central nervous system functional issue (ref)

Unfortunately there is still considerable societal and even medical stigma attached to disorders without demonstrable, measurable pathology. It is therefore understandable in this context that many patients with chronic widespread pain and generalised hypermobility find the latter a more acceptable diagnostic label.

There are problems with this however, as it could prevent patients accessing input which may otherwise help, for example self-management strategies for FM are designed to take advantage of brain plasticity which may be able to ‘train the brain’ and thereby reduce the pain burden.

It would seem sensible therefore that where patients have a fibromyalgia presentation associated with generalised hypermobility that both diagnoses are applied. This would help patients access most help.

References

Bascom R, Schubart JR, Mills S, Smith T, Zukley LM, Francomano CA, McDonnell N. Heritable disorders of connective tissue: Description of a data repository and initial cohort characterization. Am J Med Genet A. 2019 Apr;179(4):552-560. doi: 10.1002/ajmg.a.61054. Epub 2019 Feb 1. PMID: 30706611; PMCID: PMC6467085.

Byers PH. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [Updated 2019 Feb 21]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1494/

Domingos Emanuel Bevilacqua, Maillard S, Ferrari J. Measuring Joint Hypermobility Using the Hospital Del Mar Criteria - A Reliability Analysis Using Secondary Data Analysis. Arch Rheum & Arthritis Res. 1(1): 2019. ARAR.MS.ID.000502.

Harjodh Singh, Marnee McKay, Jennifer Baldwin, Leslie Nicholson, Cliffton Chan, Joshua Burns, Claire E Hiller, Beighton scores and cut-offs across the lifespan: cross-sectional study of an Australian population, Rheumatology, Volume 56, Issue 11, November 2017, Pages 1857–1864, https://doi.org/10.1093/rheumatology/kex043

Islam M, Chang C, Gershwin ME. Ehlers-Danlos Syndrome: Immunologic contrasts and connective tissue comparisons. J Transl Autoimmun. 2020 Dec 20;4:100077. doi: 10.1016/j.jtauto.2020.100077. PMID: 33437956; PMCID: PMC7786113.

Kohn, A., Chang, C. The Relationship Between Hypermobile Ehlers-Danlos Syndrome (hEDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS). Clinic Rev Allerg Immunol 58, 273–297 (2020). https://doi.org/10.1007/s12016-019-08755-8

Malek S, Reinhold EJ, Pearce GS. The Beighton Score as a measure of generalised joint hypermobility. Rheumatol Int. 2021 Oct;41(10):1707-1716. doi: 10.1007/s00296-021-04832-4. Epub 2021 Mar 18. PMID: 33738549; PMCID: PMC8390395.

https://mft.nhs.uk/gp-area-rheumatology-wtwa/

https://www.sheffieldachesandpains.com/

https://www.sheffieldachesandpains.com/joint/professional-resources/joint-hypermobility/should-i-refer-my-patient-with-hypermobility

https://www.sheffieldachesandpains.com/assets/uploads/Hypermobile_EDS_and_HSD_leaflet.pdf

https://www.sheffieldachesandpains.com/assets/2019%20genetics%20leaflet%20for%20HSD.pdf

https://www.annabelleschallenge.org/vascular-eds/eds-national-diagnostic-service#:~:text=The%20service%20sees%20patients%20who,not%20seen%20in%20this%20clinic.

https://marfan.org/dx/score/

Lucy Norcliffe-Kaufmann, Jose-Alberto Palma, Jose Martinez, Celeste Camargo, Horacio Kaufmann, Fear conditioning as a pathogenic mechanism in the postural tachycardia syndrome, Brain, Volume 145, Issue 11, November 2022, Pages 3763–3769, 

https://doi.org/10.1093/brain/awac249

https://www.hopkinsmedicine.org/health/conditions-and-diseases/postural-orthostatic-tachycardia-syndrome-pots

https://www.youtube.com/watch?v=S1HNoEpYV-I (Standing test for POTS)

https://www.ehlers-danlos.org/information/vascular-ehlers-danlos-syndrome/

https://www.ouh.nhs.uk/services/referrals/genetics/documents/eds-referral-pathway.pdf

https://www.youtube.com/watch?v=5ZJzXrgN0gE Dr Nigel Burrows

https://emedicine.medscape.com/article/943567-clinical Genetics of Ehlers-Danlos Syndrome Clinical Presentation

Updated: Apr 07, 2021 

• Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD and more

Paige SL, Lechich KM, Tierney ESS, Collins RT 2nd. Cardiac involvement in classical or hypermobile Ehlers-Danlos syndrome is uncommon. Genet Med. 2020 Oct;22(10):1583-1588. doi: 10.1038/s41436-020-0856-8. Epub 2020 Jun 9. PMID: 32518415.

Rauser-Foltz KK, Starr LJ, Yetman AT. Utilization of echocardiography in Ehlers-Danlos syndrome. Congenit Heart Dis. 2019 Sep;14(5):864-867. doi: 10.1111/chd.12824. Epub 2019 Jul 22. PMID: 31328377.

Ritter A, Atzinger C, Hays B, James J, Shikany A, Neilson D, Martin L, Weaver KN. Natural history of aortic root dilation through young adulthood in a hypermobile Ehlers-Danlos syndrome cohort. Am J Med Genet A. 2017 Jun;173(6):1467-1472. doi: 10.1002/ajmg.a.38243. Epub 2017 Apr 24. PMID: 28436618.

Stembridge N, Doolan BJ, Lavallee ME, Hausser I, Pope FM, Seneviratne SL, Winship IM, Burrows NP. The role of cutaneous manifestations in the diagnosis of the Ehlers-Danlos syndromes. Skin Health Dis. 2022 Jul 15;3(1):e140. doi: 10.1002/ski2.140. PMID: 36751332; PMCID: PMC9892481.

Gout is a condition that can be managed in primary care.

Treatment of gout flare

Use either of colchicine, NSAIDs or short course steroid for the treatment of acute attack of gout. 

• Any NSAIDs can be used. Please be aware of contraindications and drug interaction. 
• In case of colchicine suggested dose is 0.5mg twice daily. Only use colchicine in case of  if within 1 to 3 days of onset of gout – I find it doesn’t work so well if gout attack started a week ago – then steroids more helpful. 
• Short course of steroid

Offer urate lowering therapy for 

• multiple or troublesome flares
• CKD stages 3 to 5 (glomerular filtration rate [GFR] categories G3 to G5)
• diuretic therapy
• tophi
• chronic gouty arthritis

• Wait for 2 -4 weeks before starting the allopurinol/ febuxostat. In case of recurrent gout flares, allopurinol can be started along with colchicine prophylaxis 0.5mg to 1mg daily
• Please assess the risk of skin reaction
• Allopurinol can be increased up to 900mg as per S. uric acid 
• Check urate every 4 weeks and titrate dose of allopurinol aiming for urate <360 
• Continue colchicine until target urate is reached 

Check whether on any diuretics (eg thiazide or furosemide) if possible, stop, thiazide switch to alternative anti-hypertensive. 

IF on anti-hypertensive medication consider switching to losartan which has some urate lowering properties AND of course advise about lifestyle factors (diet and alcohol)

Key messages to patients

• it takes time to suppress the urate and patients need to work in partnership with their GP to check the bloods and titrate the dose 
• patients can continue to have attacks for 12 months after adequate suppression of the urate  
• allopurinol can trigger an acute attack, which is why we give the colchicine cover

USE OF FEBUXOSTAT IN GOUT

New evidence suggests both allopurinol and febuxostat can be used as main agents for lowering urate. Concerns about febuxostat's cardiovascular risk from the CARES trial have been addressed by the recent FAST trial, showing febuxostat is non inferior to allopurinol. The latest update from the Medicines and Healthcare products Regulatory Agency update (May 2023) is, in patients with pre-existing major cardiovascular diseases, febuxostat therapy should be used cautiously, particularly in those with evidence of high urate crystal and tophi burden or those initiating urate-lowering therapy. 

Therefore, in the patient as allopurinol is not suitable, febuxostat may be used cautiously. 

Most cases of gout can be safely treated in primary care.

Diagnosis

Measure serum urate

• Diagnosis of gout confirmed if the serum urate more that 360 micromol/ L

• In case of urate level less than 360 micromol/ L repeat urate levels at least 2 weeks after flare has settled 

Rheumatology referral needed only if:

• Diagnosis of gout is uncertain
• Treatment is contraindicated / ineffective / not tolerated
• CKD stage 3b – 5 ( GFR categories G3b- G5)
• They have had an organ transplant

Management of gout

General

• Patient education
• Assess risk factors
  • Obesity
  • Medicines - diuretics
  • Systemic hypertension
  • CKD
• Stress on diet and alcohol

Treatment of gout flares

• Rest
• Elevation
• Icing
• Use one of three options of drugs:
  • NSAIDS (add PPI if appropriate)
  • Colchicine (0.5mg twice daily)
  • Steroid (oral short course/intraarticular steroid if available for monoarthritis)

Offer Urate lowering therapy if:

• Multiple/troublesome flares
• CKD stage 3-5
• Diuretic therapy
• Tophi
• Chronic gouty arthritis

Urate lowering therapy

• Start after 2 weeks of last flare of gout 
• Start either Allopurinol or febuxostat 
• Use allopurinol as first line in case of major cardiovascular risk

Prevention of flares

• Discuss the benefit and risk of treatment to prevent flares 
• In patients who chose to take medicine for gout – initiate colchicine 0.5mg – 1mg at least for 3 months. 
• If colchicine is contraindicated use low dose NSAIDs or low dose steroid 

Treat to target

• Monthly uric acid and optimisation of therapy to a uric acid level of <360micromol/ L 
• Lower urate level target of <300 micromol/ L in case of 
  • Tophi / chronic gouty arthritis 
  • Ongoing frequent flares despite of urate value <360 micromol /L 
• Once target achieved – annual urate measurement 
   

Note to referrer. 

The Rheumatology department offers management for osteoporosis associated with inflammatory rheumatic diseases. For patients with osteoporosis not linked to inflammatory rheumatic disease, please refer to the endocrinology or orthogeriatrics departments.

Criteria for referral to rheumatology for osteoporosis: 

• Patients with inflammatory rheumatic disease 
• Failure/ contraindication for oral bisphosphonates 

In case of intolerance alendronate, please try risedronate (which causes slightly less in the way of GI side effects than alendronate) before considering parenteral options if there is no contraindication. 

Glucocorticoid induced osteoporosis

Bone protections should be started without waiting for DXA in patients who has been started on glucocorticoids with following criteria:

• Anyone with prior fragility fracture 
• Women ≥ 70years 
• Postmenopausal women, and men age ≥50 years, prescribed high doses of glucocorticoids, i.e., ≥7.5 mg/day of prednisolone or equivalent over 3 months (N.B., this is equivalent to ≥30mg/day of prednisone for 4 weeks over 3 months) 
• Postmenopausal women, and men age ≥50 years, with a FRAX probability of major osteoporotic fracture or of hip fracture exceeding the intervention threshold

Measurement of BMD to assess treatment response

• Please measure the FRAX score with BMD after 5 years of treatment with bisphosphonates
• If the FRAX score is above the NOGG intervention threshold or the T score is < -2.5, please continue treatment for an additional 5 years
• It is important to note that there might be some decline in the T score with age, and treatment results in a less rapid decline in BMD

PMR is a condition that can be managed in primary care.

PMR can be easily diagnosed with history of core symptoms, high inflammatory markers and a good response to steroid.

Please find the core inclusion and exclusion criteria:

I assume that the patient has been examined and this is essential. 

Investigation suggested are:  FBC, ESR, CRP, Renal and liver function test, protein electrophoresis, bone profile, TSH, CK, RF (ANA and anti CCP if inflammatory arthritis is suspected) and chest Xray may be required. 

PMR can be diagnosed with normal inflammatory markers if there is a classic clinical picture and response to steroids.

In patients with suspected PMR please consider a trial of prednisolone 15mg daily, review after 2 weeks to check response (also repeat ESR and CRP) would expect a dramatic improvement within 2-3 days. Continue same dose of steroid until symptoms are well controlled, usually 3 weeks. Please follow the flow chart for further tapering of steroid. 

Please add PPI and Ca/VitD and would refer for DXA to determine if additional bone protection needed.

Manage patient expectations:

• will be on steroids 1-2 yrs
• 1/3 of patients will flare, 1/3 will need a steroid sparing agent

Consider referral to rheumatology in case of:

• Atypical features like normal inflammatory markers 
• Lack of shoulder involvement 
• Poor response to steroids 
• Not possible to reduce corticosteroids at reasonable intervals without causing relapse
• Corticosteroids are required for more than 2 years
• anti-CCP / high positive RF or swollen peripheral joints

Please correspond via A&G in these situations to prioritise the patient being seen in the department.

Most of the Polymyalgia rheumatica can be treated in primary care.

Diagnosis

Confirm the diagnosis by: 

• Core features of PMR 

• Exclusion of differential diagnosis like RA and fibromyalgia 

• Good response to oral steroid within a week 

• Normalisation of inflammatory markers within 4 weeks

When to refer PMR to rheumatology

• Atypical features like normal inflammatory markers
• Lack of shoulder involvement 
• Poor response to steroids 
• Not possible to reduce corticosteroids at reasonable intervals without causing relapse.
• Corticosteroids are required for more than 2 years
• Positive ACCP/ high positive rheumatoid factor / peripheral joint swelling

Management of PMR

Add bone protection along with steroids without waiting for BMD in case of:

• Prior fragility fracture 
• Women aged ≥ 70 years 
• Postmenopausal women, and men age ≥50 years, prescribed high doses of glucocorticoids, i.e., ≥7.5 mg/day of prednisolone or equivalent over 3 months (N.B., this is equivalent to ≥30mg/day of prednisone for 4 weeks over 3 months) 

Start Calcium vitamin D for all and measure DEXA – to start bisphosphonates Postmenopausal women, and men age ≥50 years, with a FRAX probability of major osteoporotic fracture or of hip fracture exceeding the intervention threshold.