Table 2 Breakdown of statements of recommendations, its individual rank, and level of agreement

1

I. Concept: Who is at risk?

Early diagnosis and assessment of fracture risks and optimum management of preventable fracture risk factors through optimum fracture liaison service is very effective in the management of osteoporosis

2a

8.92 ± 0.282

H

2

Fracture liaison services improve outcomes of osteoporosis-related fractures and reductions in re-fracture incidence and mortality

2a

8.83 ± 0.482

H

3

II. Diagnosis

BMD testing is the gold standard in diagnosing osteoporosis and can be considered to stratify the patients according to their fracture risk

1a

8.67 ± 0.637

H

4

Diagnostic assessment of individuals with osteoporosis should include not only the assessment of BMD but also the exclusion of diseases that mimic osteoporosis, elucidation of the cause of the osteoporosis, and the management of any associated morbidity

2a

8.88 ± 0.338

H

5

III. Case identification

FRAX is an important web-based tool in the assessment of fragility fracture risk in osteoporosis and should be used to stratify the patients according to their fracture risk

1a

8.83 ± 0.482

H

6

It is advisable to calculate the FRAX score according to the validated Egyptian measures

1a

8.96 ± 0.204

H

7

If no Egyptian measures are available, the FRAX can be calculated according to regional validated measures

1a

8.83 ± 0.597

H

8

Adjustment of the conventional FRAX estimates of probabilities of hip fracture and a major osteoporotic fracture should be carried out to modulate the risk assessment whenever appropriate

2b

8.38 ± 0.875

H

9

Whom to treat

Postmenopausal women at high risk of fractures, especially those who have experienced a recent fracture should be assessed for osteoporosis (assessment and management of any other cofactors or comorbidities that aggravates patients fracture risks should be considered)

2a

8.92 ± 0.408

H

10

Women and men with a T score in the osteopenic range (T score − 1 to − 2.5) may still need treatment if they have been identified to have a high or very high fracture risk

2b

8.63 ± 0.824

H

11

Who should treat osteoporosis

Several specialists have the experience in managing osteoporosis including rheumatology, geriatric, ortho-geriatric medicine, and endocrinology. For a healthcare practitioner to be recognised as osteoporosis specialist, he/she should be (1) Working in National/University Hospital/Ministry of Health hospital with regular meetings and provided services. 2) In solo practice if less than 3 years, a log book showing traceable management and outcome management over 3 years. And if practice more than 3 years, the specialist should provide an audit comparing his service with gold standards as national guidelines for the treatment of osteoporosis showing the outcome of his service. (3) Preferable if healthcare professional have publications in peer-reviewed journal whether national or international

5

8.38 ± 1.056

H

12

Case stratification and intervention thresholds

Patients should be stratified according to their risk of fracture, low, moderate, high, and very high risk

2b

8.75 ± 0.608

H

13

‘Low risk’ includes no prior hip or spine fractures, a BMD T score at the hip and spine both above − 1.0, and 10-year hip fracture risk < 1% and 10-year risk of major osteoporotic fractures < 10%

2b

8.46 ± 0.932

H

14

‘Moderate risk’ includes no prior hip or spine fractures, a BMD T-score at the hip and spine both between − 1 and − 2.5, or 10-year hip fracture risk < 3% or risk of major osteoporotic fractures < 20%

2b

8.46 ± 0.932

H

15

‘High risk’ includes a prior spine or hip fracture, or a BMD T score at the hip or spine of − 2.5 or below, or 10-year hip fracture risk > 3%, or risk of major osteoporotic fracture risk > 20%

1

8.63 ± 0.824

H

16

‘Very high risk’ includes multiple spine fractures and a BMD T score at the hip or spine of − 2.5 or below

2a

8.54 ± 0.932

H

17

Very high fracture risk patients should be treated only by a specialist in osteoporosis management.

2b

8.79 ± 0.509

H

18

Falls risk

Falls risk should be assessed for every patient evaluated for fracture risk

2a

8.63 ± 0.77

H

19

Treat-to-target

Treatment target: T score > − 1.5; fracture risk below the treatment threshold or FRAX major osteoporosis fracture probability < 10%, hip fracture risk probability < 3%; fracture-free interval of 3 to 5 years

2b

8.38 ± 0.992

H

20

Investigations

Clinical: height should be measured every 1–2 years in adults ≥ 50 years of age

Biochemical tests:

Bone profile: calcium, alkaline phosphatase, eGFR, creatinine

Whenever indicated:

- 25-hydroxyvitamin D: symptoms of vitamin D deficiency

- Parathyroid hormone (PTH): persistent hypercalcaemia

- Serum testosterone, LH, FSH and SHBG, PSA (men)

- 24-h urinary cortisol/dexamethasone suppression test

- Endomysial and/or tissue transglutaminase antibodies (coeliac disease)

2a

8.58 ± 0.776

H

21

Radiological:

Assessment for presence of vertebral fracture(s) either by:

- X-ray,

- DXA-based Vertebral fracture assessment (VFA), or

- Other radiological investigations such as CT or MRI are of value particularly for vertebral fracture assessment

2a

8.58 ± 0.776

H

22

Management

Patient education/group therapy can be of value in osteoporosis management. Shared decision-making tools might be a preferable option to ensure patient compliance and adherence to therapy

1

8.59 ± 0.775

H

23

Lifestyle measures that are very important in improving bone health include increasing levels of physical activity and perform weight-bearing exercise, stopping smoking and alcohol intake, reducing the risk of falls, care for other relevant comorbidities as renal or ischaemic cardiovascular diseases, considering hip protectors, and ensuring adequate dietary calcium intake and vitamin D status

1

8.63 ± 0.711

H

24

Exercise is important for managing osteoporosis, with appropriate safety precautions

2a

8.54 ± 0.779

H

25

Every patient should be taking calcium (1 g/day) and vitamin D (1000 IU/day) supplement therapy in addition to the osteoporosis medication. The dose can be adjusted to the patient-associated comorbidities. The vitamin D dose should also be adjusted according to the serum vitamin D level

1

8.55 ± 0.932

H

26

Oral bisphosphonates (alendronate, risedronate) are first-line treatments in the majority of osteoporosis cases. Ibandronate is not recommended to reduce nonvertebral or hip fracture risk

1

8.08 ± 1.316

H

27

Patients aged ≥ 65 years with osteopaenia (T score from − 1 to − 2.5 at either the total hip or the femoral neck on either side) who have moderate risk of fracture (10-year fracture probability at the hip in the range of 1–3% and 10–20% at the spine) can be eligible to receive prophylactic treatment zoledronic acid 5 mg IV every 18 months for 4 doses

2b

8.67 ± 0.761

H

28

In osteoporotic women who are intolerant of oral bisphosphonates or in whom they are contraindicated; intravenous bisphosphonates or denosumab provide the most appropriate alternatives as initial therapy (with raloxifene or hormone replacement therapy as additional options); however, this should be decided and prescribed by osteoporosis specialist

2a

8.88 ± 0.448

H

29

Oral and intravenous bisphosphonates are contraindicated in patients with hypocalcaemia, hypersensitivity to bisphosphonates, and severe renal impairment (eGFR ≤ 35 ml/min for alendronate and zoledronic acid and ≤ 30 ml/min for other bisphosphonates). Pregnancy and lactation are also contraindications. Oral bisphosphonates are contraindicated in people with abnormalities of the oesophagus that delay oesophageal emptying such as stricture or achalasia, and inability to stand or sit upright for at least 30–60 min. They should be used with caution in patients with other upper gastrointestinal disorders. Pre-existing hypocalcaemia must be investigated and, where due to vitamin D deficiency, treated with vitamin D before treatment is initiated.

2a

8.5 ± 0.834

H

30

IV zoledronate should be prescribed and administered only by osteoporosis specialist when used for osteoporosis management.

2b

8.67 ± 0.868

H

31

Denosumab is contraindicated in women with hypocalcaemia or with hypersensitivity to any of the constituents of the formulation. Its use is not recommended in pregnancy or in the paediatric population (age ≤ 18 years).

2a

8.67 ± 0.917

H

32

Monitoring of calcium levels should be conducted prior to each dose of denosumab and within 2 weeks after the initial dose in patients predisposed to hypocalcaemia (e.g. patients with severe renal impairment, creatinine clearance ≤ 30 ml/min) or if suspected symptoms of hypocalcaemia occur or if otherwise indicated. Patients should be advised to report symptoms of hypocalcaemia.

2a

8.42 ± 1.213

H

33

Osteoporotic women age < 60 years old and less than 10 years past menopause and low thrombosis risk, who are intolerant to bisphosphonates and denosumab can be considered for HRT or SERM

- If with vasomotor symptoms and low cancer breast risk, HRT can be used

- If no uterus: oestrogen

- If uterus is present: oestrogen + progesterone

- If without vasomotor symptoms and high cancer breast risk, SERM should be used

2b

8.83 ± 0.482

H

34

In postmenopausal women with osteoporosis at very high risk of fracture, particularly those with history of osteoporotic vertebral fracture, sequential therapy can be adopted with teriparatide treatment up to 2 years is recommended then continue with anti-resorptive drug (bisphosphonates or denosumab). This should be decided and prescribed by osteoporosis specialist

2a

8.71 ± 0.69

H

35

Sequential therapy starting with romosozumab is an option for treatment of osteoporosis in postmenopausal women who are at very high risk for fracture particularly those who have past history of hip or vertebral fractures. This should be decided and prescribed by osteoporosis specialist

2a

8.54 ± 0.833

H

36

After stopping long-term denosumab therapy, patients should be switched to another antiresorptive agent to maintain the benefit achieved with denosumab (1 dose of zoledronic acid given 7–8 months after the last denosumab dose (another IV zolerdronate dose may be considered in 1 year) or oral bisphosphonate starting 6 months after the last dose of denosumab for 12–24 months may be the preferred clinical strategy)

2a

8.67 ± 0.799

H

37

Combination therapy of parathyroid hormone and denosumab can be considered in very high fracture risk patients. This should be considered on an individual basis; patients should be assessed and managed by osteoporosis specialist

2b

8.38 ± 1.056

H

38

In postmenopausal women with osteoporosis at high risk of fracture and (with a low risk of deep vein thrombosis and bisphosphonates or denosumab are not appropriate, or with a high risk of breast cancer), raloxifene may be an option

2b

8.58 ± 0.776

H

39

It is important that osteoporotic patients should always be counselled regarding treatment compliance and any side effects at 3 months after initiating therapy and then on yearly basis

2a

8.71 ± 0.624

H

40

In patients with dental disease or other risk factors (e.g. glucocorticoids, tobacco use), dental examination with preventive dentistry is recommended prior to treatment with oral or intravenous bisphosphonates

2a

8.42 ± 1.101

H

41

Whilst on bisphosphonate or denosumab therapy, patients should avoid invasive dental procedures if possible

2b

8.75 ± 0.608

H

42

Optimum treatment duration

Bisphosphonate treatment should last for 3–5 years (3 years for zoledronic acid and 5 years for alendronate and risedronate) can generally be recommended. Continuation of oral bisphosphonate (alendronate and risedronate) treatment beyond 5 years can generally be recommended in the following situations:

- Age ≥ 75 years

- Previous history of a hip or vertebral fracture

- Current treatment with oral glucocorticoids ≥ 7.5 mg prednisolone/day or equivalent

- Occurrence of one or more low trauma fractures during treatment, after exclusion of poor adherence to treatment (e.g. less than 80% of treatment has been taken) and after causes of secondary osteoporosis have been excluded. In such cases, class switching may be considered

2a

8.46 ± 0.833

H

43

Denosumab therapy should initially last for 5 years

2a

8.5 ± 0.885

H

44

Whenever indicated, the following therapies can be continued for:

•10 years—alendronic acid and denosumab

•7 years—risendronic acid

•3 years—zolendronic acid

1

8.75 ± 0.676

H

45

Parathyroid hormone therapy 20 μg daily for a maximum duration of treatment of 24 months (course not to be repeated)

2a

8.58 ± 0.974

H

46

Romosozumab therapy should last for 12 months

2a

8.59 ± 0.829

H

47

Monitoring

BMD testing can be used to monitor response to therapy

2b

8.13 ± 1.262

H

48

FRAX can be used to monitor response to therapy

5

8.66 ± 0.702

H

49

Check adherence within 3 months and yearly thereafter, including tolerability, new cautions and contraindications, calcium/vitamin D intake, change in fracture, and fall risks

2b

8.67 ± 0.702

H

50

In the case of oral bisphosphonate or denosumab, repeat BMD measurement should be carried out after initial 2 years of osteoporosis therapy to assess the response to treatment and then at 5 years when the patient completes the treatment course. In the case of IV zoledronate, repeat DXA scan should be carried out after 3 years of therapy

2a

8.83 ± 0.565

H

51

At the repeat BMD assessment carried out 2 years after starting osteoporosis therapy, good response to treatment is identified if there is increase (increase of the BMD above the precision error) or stability of BMD without the occurrence of low trauma fracture.

1

8.66 ± 0.637

H

52

Treatment failure is considered when the BMD falls significantly from baseline (by more than the precision error) or if further fractures took place despite an adequate trial and adherence to drug treatment. However, it is important to realise that even the best treatments will only decrease the fracture rate

2a

7.96 ± 1.398

H

53

Patients should continue to receive the same treatment for osteoporosis during the initial 2 years of treatment even if they experience a fragility fracture

2a

8.63 ± 0.969

H

54

If a patient remains at high fracture risk or develop a fragility fracture after 2 years of being on the same treatment, in spite of good adherence to therapy and after exclusion of secondary causes, then consider switching to another therapy

2a

8.79 ± 0.588

H

55

If a patient has a new fracture, during their treatment break, they should be reassessed immediately

2a

8.83 ± 0.381

H

56

During treatment, all patients should be encouraged to maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms such as dental mobility, pain, or swelling

2b

8.96 ± 0.204

H

57

During treatment, patients should be advised to report any thigh, hip, or groin pain and any patient presenting with such symptoms should be evaluated for an atypical femur fracture

2b

8.79 ± 0.588

H

58

During treatment with bisphosphonate or denosumab, patients should be advised to report jaw pain, swelling, or gum infections; development of exposed bone in the mouth along either the top or bottom jaws; loosening of teeth; poor healing of the gums especially after dental work, or numbness or a feeling of heaviness in the jaw

2b

8.75 ± 0.532

H

59

Drug Holiday

Drug holiday can be considered after completing 5 years of oral bisphosphonate/denosumab therapy or 3 years of zoledronate IV therapy if the target of treatment has been achieved

2a

8.46 ± 0.78

H

60

Patients with low to moderate fracture risk: consider giving bisphosphonate then stopping for a drug holiday

2a

8.67 ± 0.702

H

61

Once a holiday has begun, fracture risk and BMD should be re-evaluated every 1 to 3 years after discontinuation. A significant drop in BMD (by more than a precision error) or increase in the fracture risk may lead to re-initiation of osteoporosis therapy, depending on the individual’s fracture risk before the 5-year maximum holiday is completed

2a

8.79 ± 0.589

H

62

- Patients on corticosteroids (≥ 7.5 mg/day) or patients who have had a vertebral fracture should not usually be considered for a treatment break

- Women and men age ≥ 70 years, with a previous fragility fracture, or taking high doses of glucocorticoids (≥ 7.5 mg/day prednisolone) should be considered for bone protective therapy, after BMD baseline assessment

- In other individuals, fracture probability should be estimated using FRAX with adjustment for glucocorticoid dose. Baseline BMD assessment is advised.

- Bone-protective treatment should be started at the onset of glucocorticoid therapy in individuals at moderate/high risk of fracture

- Alendronate and risedronate are first-line treatment options. Where these are contraindicated or not tolerated, zoledronic acid, teriparatide, or denosumab (in order) are alternative options

- Bone-protective therapy may be appropriate in some premenopausal women and younger men, particularly in individuals with a previous history of fracture or receiving high doses of glucocorticoids

- For women in the childbearing period: the first-line therapy is an oral bisphosphonate; second-line therapy is a parathyroid hormone

2a

8.5 + 0.781

H

63

Osteoporosis in men

- Osteoporosis screening in men should be carried out in the age of 70 years or older

- Men at age less than 70 years old can be assessed for osteoporosis if they develop risk factors

- Men with osteopaenia (T score from − 1 to − 2.5) who have moderate risk of fracture FRAX fracture risk probability 1–3% at the hip and 10–20% at spine may be good candidates for prophylactic zoledronic acid every 18 months for 4 infusions

- For the purposes of FRAX calculations, the BMD T scores in men are calculated based on the female reference database

- Secondary causes of osteoporosis are commonly found amongst men, so this population requires thorough investigation

- Intervention thresholds for men are similar to those recommended for women

- All men starting on androgen deprivation therapy should have their fracture risk assessed

- Consider referring men with osteoporosis to specialist centres, particularly younger men or those with severe disease

- Men are assessed and treated following the same management protocol suggested above for postmenopausal women, excluding the HRT

2a

8.66 ± 0.637

H

64

Post-fracture care and Fracture Liaison service

Fracture Liaison Services (FLS) should be provided for all patients sustaining a fragility fracture:

- Ensure treatment initiation within 16 weeks of fracture

- FLS should be patient-centred and integrated between orthopaedic surgery, orthogeriatrics, rheumatology, and osteoporosis centres of care. Physicians should follow up patients at 4 and 12 months to review the use of medications that increase the risk of falls and/or fracture, to ensure co-prescription of calcium and vitamin D with bone protective interventions and to monitor adherence to therapy

2a

8.67 ± 0.868

H